Baricitinib supplier | CasNO.1187594-09-7

Name
Baricitinib
EINECS 691-421-4
CAS No. 1187594-09-7
Article Data14
CAS DataBase
Density 1.6±0.1 g/cm³
Solubility
Melting Point
Formula C₁₆H₁₇N₇O₂S
Boiling Point
Molecular Weight 371.423
Flash Point
Transport Information
Appearance
Safety
Risk Codes
Molecular Structure
Hazard Symbols
Synonyms INCB 028050;LY 3009104;1-(Ethylsulfonyl)-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]-3-azetidineacetonitrile;
PSA 128.94000
LogP 2.11438

Synthetic route

: 2-(1-(ethanesulfonyl)-3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl)azetidine-3-yl)acetonitrile

: 3680-69-1
4-chloro-1H-pyrrolo[2,3-d]pyrimidine

: 1187594-09-7
Baricitinib

Conditions

Conditions	Yield
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate In 1,4-dioxane; water at 80 - 85℃; for 5h;	99%
With tetrakis(triphenylphosphine) palladium(0); cesium fluoride In water; toluene; tert-butyl alcohol at 100℃; for 48h; Concentration; Temperature; Solvent; Reagent/catalyst; Suzuki Coupling; Inert atmosphere;	90%
With potassium phosphate; dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2 In tetrahydrofuran; water at 90℃; for 19h; Autoclave; Inert atmosphere;	90%
With tetrakis(triphenylphosphine) palladium(0); cesium fluoride In water; toluene; tert-butyl alcohol for 48h; Suzuki Coupling; Reflux; Inert atmosphere;	84%

: tert-butyl 4-{1-[3-(cyanomethyl)-1-(ethylsulfonyl)azetidin-3-yl]-1H-pyrazol-4-yl}-7H-pyrrolo[2.3-d]pyrimidine-7-carboxylate

: 1187594-09-7
Baricitinib

Conditions

Conditions	Yield
With hydrogenchloride In ethanol at 40 - 45℃;	93%
With hydrogenchloride In ethanol at 40 - 45℃;	93%
In water; butan-1-ol at 90℃;	92.7%

: 1187595-85-2
2-[1-(ethanesulfonyl)azetidin-3-ylidene]acetonitrile

: C14H15N5O2

: 1187594-09-7
Baricitinib

Conditions

Conditions	Yield
Stage #1: C14H15N5O2 With potassium carbonate In acetonitrile at 20℃; for 0.5h; Stage #2: 2-[1-(ethanesulfonyl)azetidin-3-ylidene]acetonitrile With 1,8-diazabicyclo[5.4.0]undec-7-ene In acetonitrile at 40℃; for 8h;	91.2%

: 1187595-90-9
(4-{1-[3-(cyanomethyl)-1-(ethylsulphonyl)azetidin-3-yl]-1H-pyrazol-4-yl}-7H-pyrrolo[2,3-d]pyrimidin-7-yl)methyl 2,2-dimethylpropanoate

: 1187594-09-7
Baricitinib

Conditions

Conditions	Yield
Stage #1: (4-{1-[3-(cyanomethyl)-1-(ethylsulphonyl)azetidin-3-yl]-1H-pyrazol-4-yl}-7H-pyrrolo[2,3-d]pyrimidin-7-yl)methyl 2,2-dimethylpropanoate With water; sodium hydroxide In tetrahydrofuran; methanol at 20℃; for 2 - 3h; Stage #2: With hydrogenchloride In tetrahydrofuran; methanol; water at 20℃; for 0.5h; pH=7 - 7.5; Product distribution / selectivity;	86%
With sodium hydroxide In tetrahydrofuran; methanol at 20 - 25℃; for 3h;	81%
With sodium hydroxide In tetrahydrofuran; methanol; water at 20 - 30℃;

: 1187594-13-3
2-(1-(ethylsulfonyl)-3-(4-(7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)azetidin-3-yl)acetonitrile

: 1187594-09-7
Baricitinib

Conditions

Conditions	Yield
Stage #1: 2-[1-ethanesulfonyl-3-[4-(7-[(2-(trimethylsilyl)ethoxy)methyl]-7H-pyrrolo[2,3-d]pyrimidine-4-yl)-1H-pyrazol-1-yl]azetidin-3-yl]acetonitrile With lithium tetrafluoroborate; water In acetonitrile at 75℃; Stage #2: With ammonium hydroxide; water In acetonitrile at 0 - 10℃; pH=9 - 10; Product distribution / selectivity;	83.8%

: 2-(1-(ethylsulfonyl)-3-(4-(7-p-tolylsulfonyl-7H-pyrrolo[2,3-d]pyrimidine-4-yl)-1H-pyrazol-1-yl)-3-azetidin-3-yl)acetonitrile

: 1187594-09-7
Baricitinib

Conditions

Conditions	Yield
With tetrabutyl ammonium fluoride In tetrahydrofuran at 50 - 55℃;	83%

: 2-(1-(ethylsulfonyl)-3-(4-(7-phenylsulfonyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)azetidin-3-yl)acetonitrile

: 1187594-09-7
Baricitinib

Conditions

Conditions	Yield
With tetrabutyl ammonium fluoride In 2-methyltetrahydrofuran Reflux;	81.2%

: C12H16BN3O2

: 2-(3-(4-bromo-1H-pyrazol-1-yl)-1-(ethylsulfonyl)azetidin-3-yl)acetonitrile

: 1187594-09-7
Baricitinib

Conditions

Conditions	Yield
With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium phosphate In water; N,N-dimethyl-formamide at 85 - 90℃; Inert atmosphere;	76%

: 2-(3-(4-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)-1H-pyrazole-1-yl)-1-(ethylsulfonyl)azetidin-3-yl)acetonitrile

: 3680-69-1
4-chloro-1H-pyrrolo[2,3-d]pyrimidine

: 1187594-09-7
Baricitinib

Conditions

Conditions	Yield
With palladium diacetate; caesium carbonate; 4,5-bis(diphenylphos4,5-bis(diphenylphosphino)-9,9-dimethylxanthenephino)-9,9-dimethylxanthene In N,N-dimethyl acetamide; water at 95 - 100℃; Inert atmosphere;	73%

: 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)azetidin-3-yl)acetonitrile dihydrochloride salt

: 594-44-5
Ethanesulfonyl chloride

: 1187594-09-7
Baricitinib

Conditions

Conditions	Yield
Stage #1: 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)azetidin-3-yl)acetonitrile dihydrochloride salt; Ethanesulfonyl chloride With N-ethyl-N,N-diisopropylamine In acetonitrile at 0 - 5℃; for 6h; Stage #2: With ammonium hydroxide In acetonitrile at 20℃; for 4h;	65%

: 3-[4-[7-(hydroxymethyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-1H-pyrazol-1-yl]-3-azetidineacetonitrile dihydrochloride

: 594-44-5
Ethanesulfonyl chloride

: 1187594-09-7
Baricitinib

Conditions

Conditions	Yield
Stage #1: 3-[4-[7-(hydroxymethyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-1H-pyrazol-1-yl]-3-azetidineacetonitrile dihydrochloride; Ethanesulfonyl chloride With N-ethyl-N,N-diisopropylamine In acetonitrile at 0 - 5℃; for 6h; Stage #2: With ammonium hydroxide In acetonitrile at 20℃; for 4h;	65%

: 1153949-11-1
3-(cyanomethylene)azetidine-1-carboxylic acid tert-butyl ester

: 1187594-09-7
Baricitinib

Conditions

Conditions	Yield
Multi-step reaction with 4 steps 1: trifluoroacetic acid / dichloromethane / 5 h / 20 °C 2: N-ethyl-N,N-diisopropylamine / acetonitrile / 0 - 20 °C 3: 1,8-diazabicyclo[5.4.0]undec-7-ene / acetonitrile; isopropyl alcohol / 4 h / 60 °C 4: tetrakis(triphenylphosphine) palladium(0); cesium fluoride / tert-butyl alcohol; water; toluene / 48 h / Reflux; Inert atmosphere View Scheme
Multi-step reaction with 4 steps 1: trifluoroacetic acid / acetonitrile / 4 h / 20 °C 2: N-ethyl-N,N-diisopropylamine / acetonitrile / 0 - 5 °C 3: 1,8-diazabicyclo[5.4.0]undec-7-ene / isopropyl alcohol / 3.5 h / 20 - 60 °C 4: cesium fluoride; tetrakis(triphenylphosphine) palladium(0) / toluene; water; tert-butyl alcohol / 48 h / 100 °C / Inert atmosphere View Scheme
Multi-step reaction with 4 steps 1.1: 1,8-diazabicyclo[5.4.0]undec-7-ene / isopropyl alcohol / Reflux 2.1: potassium carbonate; tetrakis(triphenylphosphine) palladium(0) / isopropyl alcohol; water / 1 h / Reflux 3.1: hydrogenchloride / isopropyl alcohol; water; methanol / 20 - 25 °C 3.2: 20 - 25 °C 4.1: N-ethyl-N,N-diisopropylamine / acetonitrile / 6 h / 0 - 5 °C 4.2: 4 h / 20 °C View Scheme
Multi-step reaction with 4 steps 1.1: 1,8-diazabicyclo[5.4.0]undec-7-ene / isopropyl alcohol / Reflux 2.1: potassium carbonate; tetrakis(triphenylphosphine) palladium(0) / isopropyl alcohol; water / 1 h / Reflux 3.1: hydrogenchloride / isopropyl alcohol; water; methanol / 20 - 25 °C 3.2: 20 - 25 °C 4.1: N-ethyl-N,N-diisopropylamine / acetonitrile / 6 h / 0 - 5 °C 4.2: 4 h / 20 °C View Scheme
Multi-step reaction with 4 steps 1.1: 1,8-diazabicyclo[5.4.0]undec-7-ene / isopropyl alcohol / Reflux 2.1: potassium carbonate; tetrakis(triphenylphosphine) palladium(0) / 1,4-dioxane; water / 1 h / Reflux 3.1: hydrogenchloride / 1,4-dioxane; water / 15 - 20 °C 4.1: N-ethyl-N,N-diisopropylamine / acetonitrile / 6 h / 0 - 5 °C 4.2: 4 h / 20 °C View Scheme

: 2-(azetidin-3-ylidene)acetonitrile

: 1187594-09-7
Baricitinib

Conditions

Conditions	Yield
Multi-step reaction with 3 steps 1: N-ethyl-N,N-diisopropylamine / acetonitrile / 0 - 20 °C 2: 1,8-diazabicyclo[5.4.0]undec-7-ene / acetonitrile; isopropyl alcohol / 4 h / 60 °C 3: tetrakis(triphenylphosphine) palladium(0); cesium fluoride / tert-butyl alcohol; water; toluene / 48 h / Reflux; Inert atmosphere View Scheme
Multi-step reaction with 3 steps 1: N-ethyl-N,N-diisopropylamine / acetonitrile / 0 - 5 °C 2: 1,8-diazabicyclo[5.4.0]undec-7-ene / isopropyl alcohol / 3.5 h / 20 - 60 °C 3: cesium fluoride; tetrakis(triphenylphosphine) palladium(0) / toluene; water; tert-butyl alcohol / 48 h / 100 °C / Inert atmosphere View Scheme

: 1187595-85-2
2-[1-(ethanesulfonyl)azetidin-3-ylidene]acetonitrile

: 1187594-09-7
Baricitinib

Conditions

Conditions	Yield
Multi-step reaction with 2 steps 1: 1,8-diazabicyclo[5.4.0]undec-7-ene / isopropyl alcohol / 3.5 h / 20 - 60 °C 2: cesium fluoride; tetrakis(triphenylphosphine) palladium(0) / toluene; water; tert-butyl alcohol / 48 h / 100 °C / Inert atmosphere View Scheme
Multi-step reaction with 2 steps 1: N,N,N′,N′-tetramethyl-N″-tert-butylguanidine / tetrahydrofuran / 3 h / 65 °C 2: dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium phosphate / water; tetrahydrofuran / 19 h / 90 °C / Autoclave; Inert atmosphere View Scheme
Multi-step reaction with 3 steps 1: N,N,N′,N′-tetramethyl-N″-tert-butylguanidine / tetrahydrofuran / 3 h / 65 °C 2: dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2 / 9 h / 60 °C 3: water; butan-1-ol / 90 °C View Scheme

: 3680-69-1
4-chloro-1H-pyrrolo[2,3-d]pyrimidine

: 1187594-09-7
Baricitinib

Conditions

Conditions	Yield
Multi-step reaction with 3 steps 1: potassium phosphate / water; tetrahydrofuran / 17 h / 20 - 25 °C 2: dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2 / 9 h / 60 °C 3: water; butan-1-ol / 90 °C View Scheme
Multi-step reaction with 6 steps 1.1: potassium tert-butylate / tetrahydrofuran / 0.33 h / 20 °C 1.2: 3 h 2.1: potassium carbonate; tetrakis(triphenylphosphine) palladium(0) / water; N,N-dimethyl-formamide / 4 h / 20 - 85 °C 3.1: 1,8-diazabicyclo[5.4.0]undec-7-ene / 14 h / 20 °C 4.1: hydrogenchloride / water; ethanol / 2 h / Reflux 5.1: N-ethyl-N,N-diisopropylamine / dichloromethane / 0 - 20 °C 6.1: tetrabutyl ammonium fluoride / 2-methyltetrahydrofuran / Reflux View Scheme
Multi-step reaction with 3 steps 1.1: dipotassium hydrogenphosphate / tetrahydrofuran; water / 12 h / 20 °C 2.1: hydrazine hydrate / 8 h / Reflux 3.1: potassium carbonate / acetonitrile / 0.5 h / 20 °C 3.2: 8 h / 40 °C View Scheme

: 1-ethylsulfonylazetidin-3-ol

: 1187594-09-7
Baricitinib

Conditions

Conditions	Yield
Multi-step reaction with 4 steps 1.1: 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical / ethyl acetate / 2 h 1.2: 3.5 h / 3 - 11 °C / Inert atmosphere 2.1: N-ethyl-N,N-diisopropylamine / isopropyl alcohol / 20 h / 0 - 10 °C 3.1: N,N,N′,N′-tetramethyl-N″-tert-butylguanidine / tetrahydrofuran / 3 h / 65 °C 4.1: dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium phosphate / water; tetrahydrofuran / 19 h / 90 °C / Autoclave; Inert atmosphere View Scheme
Multi-step reaction with 5 steps 1.1: 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical / ethyl acetate / 2 h 1.2: 3.5 h / 3 - 11 °C / Inert atmosphere 2.1: N-ethyl-N,N-diisopropylamine / isopropyl alcohol / 20 h / 0 - 10 °C 3.1: N,N,N′,N′-tetramethyl-N″-tert-butylguanidine / tetrahydrofuran / 3 h / 65 °C 4.1: dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2 / 9 h / 60 °C 5.1: water; butan-1-ol / 90 °C View Scheme
Multi-step reaction with 4 steps 1: sulfur trioxide pyridine complex; triethylamine / dichloromethane / -5 - 20 °C 2: dichloromethane / 20 °C 3: 1,8-diazabicyclo[5.4.0]undec-7-ene / acetonitrile / 35 - 40 °C 4: palladium diacetate; 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene; caesium carbonate / water; N,N-dimethyl acetamide / 95 - 100 °C / Inert atmosphere View Scheme
Multi-step reaction with 5 steps 1: sulfur trioxide pyridine complex; triethylamine / dichloromethane / -5 - 20 °C 2: dichloromethane / 20 °C 3: 1,8-diazabicyclo[5.4.0]undec-7-ene / acetonitrile / 35 - 40 °C 4: palladium diacetate; tricyclohexylphosphine; potassium phosphate / water; 1,4-dioxane / 90 - 100 °C / Inert atmosphere 5: hydrogenchloride / ethanol / 40 - 45 °C View Scheme
Multi-step reaction with 5 steps 1: sulfur trioxide pyridine complex; triethylamine / dichloromethane / -5 - 20 °C 2: dichloromethane / 20 °C 3: 1,8-diazabicyclo[5.4.0]undec-7-ene / acetonitrile / 35 - 40 °C 4: palladium diacetate; 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene; caesium carbonate / water; Isopropyl acetate / 95 - 100 °C 5: tetrabutyl ammonium fluoride / tetrahydrofuran / 50 - 55 °C View Scheme

: 1-(ethylsulfonyl)azetidin-3-one

: 1187594-09-7
Baricitinib

Conditions

Conditions	Yield
Multi-step reaction with 3 steps 1: N-ethyl-N,N-diisopropylamine / isopropyl alcohol / 20 h / 0 - 10 °C 2: N,N,N′,N′-tetramethyl-N″-tert-butylguanidine / tetrahydrofuran / 3 h / 65 °C 3: dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium phosphate / water; tetrahydrofuran / 19 h / 90 °C / Autoclave; Inert atmosphere View Scheme
Multi-step reaction with 4 steps 1: N-ethyl-N,N-diisopropylamine / isopropyl alcohol / 20 h / 0 - 10 °C 2: N,N,N′,N′-tetramethyl-N″-tert-butylguanidine / tetrahydrofuran / 3 h / 65 °C 3: dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2 / 9 h / 60 °C 4: water; butan-1-ol / 90 °C View Scheme
Multi-step reaction with 3 steps 1: piperidine / toluene / Reflux 2: 1,8-diazabicyclo[5.4.0]undec-7-ene / acetonitrile / 35 - 40 °C 3: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium phosphate / N,N-dimethyl-formamide; water / 85 - 90 °C / Inert atmosphere View Scheme

: C10H13IN4O2S

: 1187594-09-7
Baricitinib

Conditions

Conditions	Yield
Multi-step reaction with 3 steps 1.1: isopropyl magnesium chloride - lithium chloride complex / tetrahydrofuran / -10 - 0 °C / Inert atmosphere 1.2: 20 °C / Inert atmosphere 2.1: palladium diacetate; caesium carbonate; CyJohnPhos / N,N-dimethyl-formamide; water / 90 - 100 °C / Inert atmosphere 3.1: hydrogenchloride / ethanol / 40 - 45 °C View Scheme

: 2-(3-(4-bromo-1H-pyrazol-1-yl)-1-(ethylsulfonyl)azetidin-3-yl)acetonitrile

: 1187594-09-7
Baricitinib

Conditions

Conditions	Yield
Multi-step reaction with 2 steps 1.1: potassium acetate; palladium diacetate; CyJohnPhos / N,N-dimethyl-formamide / 60 - 65 °C / Inert atmosphere 1.2: 95 - 100 °C / Inert atmosphere 2.1: hydrogenchloride / ethanol / 40 - 45 °C View Scheme
Multi-step reaction with 3 steps 1: potassium acetate; (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride / tetrahydrofuran / 60 - 65 °C / Inert atmosphere 2: palladium diacetate; caesium carbonate; CyJohnPhos / N,N-dimethyl-formamide; water / 90 - 100 °C / Inert atmosphere 3: hydrogenchloride / ethanol / 40 - 45 °C View Scheme

: 2-(1-(ethanesulfonyl)-3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl)azetidine-3-yl)acetonitrile

: 1187594-09-7
Baricitinib

Conditions

Conditions	Yield
Multi-step reaction with 2 steps 1: palladium diacetate; caesium carbonate; CyJohnPhos / N,N-dimethyl-formamide; water / 90 - 100 °C / Inert atmosphere 2: hydrogenchloride / ethanol / 40 - 45 °C View Scheme

: N-(3-chloro-2-hydroxypropyl)ethane sulfonamide

: 1187594-09-7
Baricitinib

Conditions

Conditions	Yield
Multi-step reaction with 5 steps 1: potassium tert-butylate / N,N-dimethyl-formamide / 0 - 20 °C 2: sulfur trioxide pyridine complex; triethylamine / dichloromethane / -5 - 20 °C 3: dichloromethane / 20 °C 4: 1,8-diazabicyclo[5.4.0]undec-7-ene / acetonitrile / 35 - 40 °C 5: palladium diacetate; 4,5-bis(diphenylphos4,5-bis(diphenylphosphino)-9,9-dimethylxanthenephino)-9,9-dimethylxanthene; caesium carbonate / water; N,N-dimethyl acetamide / 95 - 100 °C / Inert atmosphere View Scheme
Multi-step reaction with 6 steps 1: potassium tert-butylate / N,N-dimethyl-formamide / 0 - 20 °C 2: sulfur trioxide pyridine complex; triethylamine / dichloromethane / -5 - 20 °C 3: dichloromethane / 20 °C 4: 1,8-diazabicyclo[5.4.0]undec-7-ene / acetonitrile / 35 - 40 °C 5: palladium diacetate; 4,5-bis(diphenylphos4,5-bis(diphenylphosphino)-9,9-dimethylxanthenephino)-9,9-dimethylxanthene; caesium carbonate / water; Isopropyl acetate / 95 - 100 °C 6: tetrabutyl ammonium fluoride / tetrahydrofuran / 50 - 55 °C View Scheme
Multi-step reaction with 6 steps 1: potassium tert-butylate / N,N-dimethyl-formamide / 0 - 20 °C 2: sulfur trioxide pyridine complex; triethylamine / dichloromethane / -5 - 20 °C 3: dichloromethane / 20 °C 4: 1,8-diazabicyclo[5.4.0]undec-7-ene / acetonitrile / 35 - 40 °C 5: palladium diacetate; tricyclohexylphosphine; potassium phosphate / water; 1,4-dioxane / 90 - 100 °C / Inert atmosphere 6: hydrogenchloride / ethanol / 40 - 45 °C View Scheme

: 2-(3-(4-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)-1H-pyrazole-1-yl)-1-(ethylsulfonyl)azetidin-3-yl)acetonitrile

: 1187594-09-7
Baricitinib

Conditions

Conditions	Yield
Multi-step reaction with 2 steps 1: palladium diacetate; tricyclohexylphosphine; potassium phosphate / water; 1,4-dioxane / 90 - 100 °C / Inert atmosphere 2: hydrogenchloride / ethanol / 40 - 45 °C View Scheme
Multi-step reaction with 2 steps 1: palladium diacetate; 4,5-bis(diphenylphos4,5-bis(diphenylphosphino)-9,9-dimethylxanthenephino)-9,9-dimethylxanthene; caesium carbonate / water; Isopropyl acetate / 95 - 100 °C 2: tetrabutyl ammonium fluoride / tetrahydrofuran / 50 - 55 °C View Scheme

: tert-butyl 3-{4-[7-(benzenesulfonyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-1H-pyrazol-1-yl}-3-(cyanomethyl)azetidine-1-carboxylate

: 1187594-09-7
Baricitinib

Conditions

Conditions	Yield
Multi-step reaction with 3 steps 1: hydrogenchloride / water; ethanol / 2 h / Reflux 2: N-ethyl-N,N-diisopropylamine / dichloromethane / 0 - 20 °C 3: tetrabutyl ammonium fluoride / 2-methyltetrahydrofuran / Reflux View Scheme

: 186519-89-1
4-chloro-7-(phenylsulfonyl)-7H-pyrrolo [2,3-d]pyrimidine

: 1187594-09-7
Baricitinib

Conditions

Conditions	Yield
Multi-step reaction with 5 steps 1: potassium carbonate; tetrakis(triphenylphosphine) palladium(0) / water; N,N-dimethyl-formamide / 4 h / 20 - 85 °C 2: 1,8-diazabicyclo[5.4.0]undec-7-ene / 14 h / 20 °C 3: hydrogenchloride / water; ethanol / 2 h / Reflux 4: N-ethyl-N,N-diisopropylamine / dichloromethane / 0 - 20 °C 5: tetrabutyl ammonium fluoride / 2-methyltetrahydrofuran / Reflux View Scheme

: 7-(phenylsulfonyl)-4-(1H-pyrazol-4-yl)-7H-pyrrolo[2,3-d]pyrimidine

: 1187594-09-7
Baricitinib

Conditions

Conditions	Yield
Multi-step reaction with 4 steps 1: 1,8-diazabicyclo[5.4.0]undec-7-ene / 14 h / 20 °C 2: hydrogenchloride / water; ethanol / 2 h / Reflux 3: N-ethyl-N,N-diisopropylamine / dichloromethane / 0 - 20 °C 4: tetrabutyl ammonium fluoride / 2-methyltetrahydrofuran / Reflux View Scheme

: 1236033-21-8
4-chloro-7H-pyrrolo[2,3-d]pyrimidine-7-carboxylic acid tert-butyl ester

: 1187594-09-7
Baricitinib

Conditions

Conditions	Yield
Multi-step reaction with 2 steps 1.1: hydrazine hydrate / 8 h / Reflux 2.1: potassium carbonate / acetonitrile / 0.5 h / 20 °C 2.2: 8 h / 40 °C View Scheme

: 67-56-1
methanol

: 1187595-90-9
(4-{1-[3-(cyanomethyl)-1-(ethylsulphonyl)azetidin-3-yl]-1H-pyrazol-4-yl}-7H-pyrrolo[2,3-d]pyrimidin-7-yl)methyl 2,2-dimethylpropanoate

A: 1187594-09-7
Baricitinib

B: 2-{1-(ethanesulfonyl)-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-3-yl}acetamide

C: 2-{1-(ethanesulfonyl)-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-3-yl}acetic acid

D: [1-(ethanesulfonyl)-3-{4-[7-(hydroxymethyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-1H-pyrazol-1-yl}azetidin-3-yl]acetonitrile

E: methyl 2-{1-(ethanesulfonyl)-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-3-yl}acetimidate

F: methyl 2-{1-(ethanesulfonyl)-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-3-yl}acetate

Conditions

Conditions	Yield
With water; lithium hydroxide In acetonitrile Inert atmosphere;

...Expand

: 1146629-77-7
[4-(1H-pyrazol-4-yl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl]methyl 2,2-dimethylpropanoate

: 1187594-09-7
Baricitinib

Conditions

Conditions	Yield
Multi-step reaction with 2 steps 1: 1,8-diazabicyclo[5.4.0]undec-7-ene / acetonitrile; N,N-dimethyl-formamide / Inert atmosphere 2: lithium hydroxide; water / acetonitrile / Inert atmosphere View Scheme

: 1146629-76-6
(4-(1-(1-ethoxyethyl)-1H-pyrazol-4-yl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)methyl pivalate

: 1187594-09-7
Baricitinib

Conditions

Conditions	Yield
Multi-step reaction with 3 steps 1: hydrogenchloride; water / tetrahydrofuran / Inert atmosphere 2: 1,8-diazabicyclo[5.4.0]undec-7-ene / acetonitrile; N,N-dimethyl-formamide / Inert atmosphere 3: lithium hydroxide; water / acetonitrile / Inert atmosphere View Scheme

: 1146629-75-5
(4-chloro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)methyl 2,2-dimethylpropanoate

: 1187594-09-7
Baricitinib

Conditions

Conditions	Yield
Multi-step reaction with 4 steps 1: tetrakis(triphenylphosphine) palladium(0); potassium carbonate / Inert atmosphere 2: hydrogenchloride; water / tetrahydrofuran / Inert atmosphere 3: 1,8-diazabicyclo[5.4.0]undec-7-ene / acetonitrile; N,N-dimethyl-formamide / Inert atmosphere 4: lithium hydroxide; water / acetonitrile / Inert atmosphere View Scheme

: 1187594-09-7
Baricitinib

: 98-11-3
benzenesulfonic acid

: {1-(ethylsulphonyl)-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-3-yl}acetonitrile besylate

Conditions

Conditions	Yield
In ethyl acetate at 20 - 22℃; for 2h; Solvent; Temperature;	100%

: 1187594-09-7
Baricitinib

: 1187595-84-1
{1-(ethylsulfonyl)-3-[4-(7H-pyrrolo[2,3-d] pyrimidin-)-1H-pyrazol-1-yl] azetidin-3-yl}acetonitrile phosphate

Conditions

Conditions	Yield
With phosphoric acid In methanol; water; acetonitrile at 68℃; for 1h; Solvent; Temperature;	99.2%
With phosphoric acid In ethanol; acetonitrile at 70℃; for 2h; Product distribution / selectivity;	93%
With phosphoric acid In ethanol; acetonitrile at 70℃; for 2h;

: 594-45-6
ethanesulfonic acid

: 1187594-09-7
Baricitinib

: {1-(ethylsulphonyl)-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-3-yl}acetonitrile esylate

Conditions

Conditions	Yield
In ethyl acetate at 20 - 22℃; for 2h; Solvent; Temperature;	98.8%

: 1187594-09-7
Baricitinib

: baricitinib hemiphosphate

Conditions

Conditions	Yield
With phosphoric acid In propan-1-ol; ethanol at 68℃; for 1.5h;	97.9%

: 75-75-2
methanesulfonic acid

: 1187594-09-7
Baricitinib

: {1-(ethylsulphonyl)-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-3-yl}acetonitrile mesylate

Conditions

Conditions	Yield
In isopropyl alcohol at 20 - 22℃; for 2h; Solvent;	97.8%

: 1187594-09-7
Baricitinib

: 104-15-4
toluene-4-sulfonic acid

: {1-(ethylsulphonyl)-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-3-yl}acetonitrile tosylate

Conditions

Conditions	Yield
In acetonitrile at 20 - 22℃; for 3h;	96.7%

: 1187594-09-7
Baricitinib

: 110-17-8
(2E)-but-2-enedioic acid

: {1-(ethylsulphonyl)-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-3-yl}acetonitrile fumarate

Conditions

Conditions	Yield
In acetonitrile for 0.5h; Reflux;	96.7%
In tetrahydrofuran for 1h;

: 107-36-8
2-hydroxyethanesulfonic acid

: 1187594-09-7
Baricitinib

: {1-(ethylsulphonyl)-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-3-yl}acetonitrile 2-hydroxyethane sulfonic acid salt

Conditions

Conditions	Yield
In acetonitrile at 20 - 22℃; for 4h;	90.8%

: 1187594-09-7
Baricitinib

: 110-17-8
(2E)-but-2-enedioic acid

: {1-(ethylsulfonyl)-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-3-yl}acetonitrile fumaric acid salt

Conditions

Conditions	Yield
In water; dimethyl sulfoxide at 5 - 60℃; Solvent; Temperature;	86%

: 1187594-09-7
Baricitinib

: baricitinib phosphate

Conditions

Conditions	Yield
With phosphoric acid In ethanol; acetonitrile at 70℃; for 2h;	80%

: 1187594-09-7
Baricitinib

: 79-30-1
isobutyryl chloride

: C20H23N7O3S

Conditions

Conditions	Yield
Stage #1: Baricitinib In dichloromethane; acetonitrile for 0.25h; Cooling with ice; Stage #2: isobutyryl chloride In dichloromethane; acetonitrile at 20℃;	72%

: 33657-49-7
chloromethyl n-butyrate

: 1187594-09-7
Baricitinib

: C21H25N7O4S

Conditions

Conditions	Yield
Stage #1: Baricitinib In dichloromethane; acetonitrile for 0.25h; Cooling with ice; Stage #2: With sodium hydride In dichloromethane; acetonitrile for 0.5h; Stage #3: chloromethyl n-butyrate In dichloromethane; acetonitrile at 20℃;	68%

: 1187594-09-7
Baricitinib

: 813-77-4
Dimethyl chlorophosphate

: C18H22N7O5PS

Conditions

Conditions	Yield
Stage #1: Baricitinib In dichloromethane; acetonitrile for 0.25h; Cooling with ice; Stage #2: With sodium hydride In dichloromethane; acetonitrile for 0.5h; Stage #3: Dimethyl chlorophosphate In dichloromethane; acetonitrile at 20℃;	68%

: 1187594-09-7
Baricitinib

: 77-92-9
citric acid

: {1-(ethylsulfonyl)-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-3-yl}acetonitrile dicitrate

Conditions

Conditions	Yield
In acetonitrile at 0℃; for 2h; Solvent; Temperature; Reflux;	67%

: 1187594-09-7
Baricitinib

: 75-36-5
acetyl chloride

: C18H19N7O3S

Conditions

Conditions	Yield
Stage #1: Baricitinib In dichloromethane; acetonitrile for 0.25h; Cooling with ice; Stage #2: acetyl chloride In dichloromethane; acetonitrile at 20℃;	64%

: 1187594-09-7
Baricitinib

: 77-92-9
citric acid

: {1-(ethylsulfonyl)-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-3-yl}acetonitrile monocitrate

Conditions

Conditions	Yield
In acetonitrile at 20℃; for 18h; Solvent; Temperature;	61%

: 1187594-09-7
Baricitinib

: 2-{1-(ethanesulfonyl)-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-3-yl}acetamide

Conditions

Conditions	Yield
With dihydrogen peroxide; sodium hydroxide In methanol; dimethyl sulfoxide at 50℃; for 3h; Temperature; Reagent/catalyst; Solvent;	58.4%

: 1187594-09-7
Baricitinib

: 144-62-7
oxalic acid

: {1-(ethylsulphonyl)-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-3-yl}acetonitrile oxalate

Conditions

Conditions	Yield
In acetonitrile at 20 - 22℃; for 2h;	56.36%

: 1187594-09-7
Baricitinib

: C16H16N7O5PS(2-)*2Na(1+)

Conditions

Conditions	Yield
With Sodium trimetaphosphate; sodium carbonate In water at 45℃;	51%

Baricitinib Specification

The Baricitinib, with the CAS registry number 1187594-09-7, is also known as 3-Azetidineacetonitrile, 1-(ethylsulfonyl)-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]-. This chemical's molecular formula is C₁₆H₁₇N₇O₂S and molecular weight is 371.42. What's more, its systematic name is {1-(Ethylsulfonyl)-3-[4-(1H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]-3-azetidinyl}acetonitrile. This chemical is an oral JAK1 and JAK2 inhibitor. It has shown encouraging results in a clinical trial for rheumatoid arthritis.

Physical properties of Baricitinib are: (1)ACD/LogP: -0.06±0.73; (2)# of Rule of 5 Violations: 0; (3)ACD/LogD (pH 5.5): -0.07; (4)ACD/LogD (pH 7.4): -0.07; (5)ACD/BCF (pH 5.5): 1.00; (6)ACD/BCF (pH 7.4): 1.00; (7)ACD/KOC (pH 5.5): 21.62; (8)ACD/KOC (pH 7.4): 21.97; (9)#H bond acceptors: 9; (10)#H bond donors: 1; (11)#Freely Rotating Bonds: 5; (12)Polar Surface Area: 128.94 Å²; (13)Index of Refraction: 1.763; (14)Molar Refractivity: 98.2±0.5 cm³; (15)Molar Volume: 238.1±7.0 cm³; (16)Polarizability: 38.9±0.5×10^-24cm³; (17)Surface Tension: 73.0±7.0 dyne/cm; (18)Density: 1.6±0.1 g/cm³.

You can still convert the following datas into molecular structure:
(1)SMILES: CCS(=O)(=O)N1CC(C1)(CC#N)n2cc(cn2)c3c4cc[nH]c4ncn3
(2)Std. InChI: InChI=1S/C16H17N7O2S/c1-2-26(24,25)22-9-16(10-22,4-5-17)23-8-12(7-21-23)14-13-3-6-18-15(13)20-11-19-14/h3,6-8,11H,2,4,9-10H2,1H3,(H,18,19,20)
(3)Std. InChIKey: XUZMWHLSFXCVMG-UHFFFAOYSA-N

Product Name

Baricitinib

Synthetic route

Baricitinib Specification

Related Products

Hot Products