5-(1-hydroxy-2-(2,4,5-trifluorophenyl)ethylidene)-2,2-dimethyl-1,3-dioxane-4,6-dione
3-(trifluoromethyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazine hydrochloride
1-(3-(trifluoromethyl)-5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl)-4-(2,4,5-trifluorophenyl)butane-1,3-dione
Conditions | Yield |
---|---|
With 4-methyl-morpholine In ethyl acetate for 6h; Reflux; | 98.1% |
With N-ethyl-N,N-diisopropylamine In Isopropyl acetate at 85℃; for 4h; | 93.3% |
With N-ethyl-N,N-diisopropylamine In Isopropyl acetate at 85℃; for 3.5h; | 92% |
3-trifluoromethyl-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazine
5-(1-hydroxy-2-(2,4,5-trifluorophenyl)ethylidene)-2,2-dimethyl-1,3-dioxane-4,6-dione
1-(3-(trifluoromethyl)-5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl)-4-(2,4,5-trifluorophenyl)butane-1,3-dione
Conditions | Yield |
---|---|
In N,N-dimethyl acetamide at 41.1℃; Kinetics; Further Variations:; Temperatures; | 91% |
4-(2,4,5-trifluorophenyl)-3-oxobutanoic acid
3-trifluoromethyl-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazine
1-(3-(trifluoromethyl)-5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl)-4-(2,4,5-trifluorophenyl)butane-1,3-dione
Conditions | Yield |
---|---|
Stage #1: 4-(2,4,5-trifluorophenyl)-3-oxobutanoic acid With oxalyl dichloride In dichloromethane at 10 - 35℃; Stage #2: 3-trifluoromethyl-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazine With triethylamine In dichloromethane at 0 - 15℃; | 91% |
cycl-isopropylidene malonate
(2,4,5-trifluorophenyl)acetic acid
3-(trifluoromethyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazine hydrochloride
1-(3-(trifluoromethyl)-5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl)-4-(2,4,5-trifluorophenyl)butane-1,3-dione
Conditions | Yield |
---|---|
Stage #1: cycl-isopropylidene malonate; (2,4,5-trifluorophenyl)acetic acid With dmap; pivaloyl chloride; N-ethyl-N,N-diisopropylamine In acetonitrile at 45 - 55℃; Large scale reaction; Stage #2: 3-(trifluoromethyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazine hydrochloride With trifluoroacetic acid In acetonitrile at 50 - 55℃; for 6h; Large scale reaction; | 90% |
Stage #1: cycl-isopropylidene malonate; (2,4,5-trifluorophenyl)acetic acid With dmap; pivaloyl chloride; N-ethyl-N,N-diisopropylamine In N,N-dimethyl acetamide at 20 - 50℃; for 2 - 3h; Stage #2: 3-(trifluoromethyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazine hydrochloride In N,N-dimethyl acetamide at 40 - 70℃; Stage #3: With sodium hydrogencarbonate In N,N-dimethyl acetamide; water at 20 - 45℃; | 89% |
Stage #1: cycl-isopropylidene malonate; (2,4,5-trifluorophenyl)acetic acid With dmap; pivaloyl chloride; N-ethyl-N,N-diisopropylamine In acetonitrile at 20 - 50℃; for 2 - 3h; Stage #2: 3-(trifluoromethyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazine hydrochloride With trifluoroacetic acid In acetonitrile at 40 - 55℃; for 6h; | |
Stage #1: cycl-isopropylidene malonate; (2,4,5-trifluorophenyl)acetic acid With dmap; pivaloyl chloride; N-ethyl-N,N-diisopropylamine In ISOPROPYLAMIDE at 0 - 40℃; for 2 - 3h; Stage #2: 3-(trifluoromethyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazine hydrochloride In ISOPROPYLAMIDE at 40 - 70℃; | |
Stage #1: cycl-isopropylidene malonate; (2,4,5-trifluorophenyl)acetic acid With dmap; N-ethyl-N,N-diisopropylamine In acetonitrile at 50℃; Stage #2: With pivaloyl chloride In acetonitrile at 50℃; for 3.75h; Stage #3: 3-(trifluoromethyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazine hydrochloride With trifluoroacetic acid In acetonitrile at 55℃; for 6h; |
1-(3-(trifluoromethyl)-5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl)-4-(2,4,5-trifluorophenyl)butane-1,3-dione
Conditions | Yield |
---|---|
With hydrogenchloride In water; ethyl acetate at 25 - 30℃; | 90% |
With hydrogenchloride In water; ethyl acetate at 25 - 30℃; for 0.5h; | 90% |
2,4,5-trifluorobenzyl bromide
1-(3-(trifluoromethyl)-5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl)-4-(2,4,5-trifluorophenyl)butane-1,3-dione
Conditions | Yield |
---|---|
Stage #1: 2,4,5-trifluorobenzyl bromide With magnesium In tetrahydrofuran at 35 - 45℃; for 2.16667h; Stage #2: 3-oxo-3-[3-(trifluoromethyl)-5,6-dihydro[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl]propanenitrile In tetrahydrofuran; toluene at 0 - 5℃; for 4h; Temperature; | 89.5% |
(2,4,5-trifluorophenyl)acetic acid
3-(trifluoromethyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazine hydrochloride
1-(3-(trifluoromethyl)-5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl)-4-(2,4,5-trifluorophenyl)butane-1,3-dione
Conditions | Yield |
---|---|
Stage #1: (2,4,5-trifluorophenyl)acetic acid With cycl-isopropylidene malonate; N-ethyl-N,N-diisopropylamine; dmap In ISOPROPYLAMIDE at 20 - 40℃; Stage #2: With pivaloyl chloride In ISOPROPYLAMIDE at 0 - 5℃; for 1 - 3h; Stage #3: 3-(trifluoromethyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazine hydrochloride In ISOPROPYLAMIDE at 40 - 70℃; | 89% |
Stage #1: cycl-isopropylidene malonate; (2,4,5-trifluorophenyl)acetic acid With dmap; pivaloyl chloride; N-ethyl-N,N-diisopropylamine In N,N-dimethyl acetamide at 0 - 40℃; for 2 - 3h; Stage #2: 3-(trifluoromethyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazine hydrochloride In N,N-dimethyl acetamide at 40 - 70℃; for 1h; |
cycl-isopropylidene malonate
3-trifluoromethyl-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazine
(2,4,5-trifluorophenyl)acetic acid
1-(3-(trifluoromethyl)-5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl)-4-(2,4,5-trifluorophenyl)butane-1,3-dione
Conditions | Yield |
---|---|
Stage #1: cycl-isopropylidene malonate; (2,4,5-trifluorophenyl)acetic acid With dmap; pivaloyl chloride; N-ethyl-N,N-diisopropylamine In N,N-dimethyl acetamide at 50 - 55℃; Stage #2: 3-trifluoromethyl-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazine With trifluoroacetic acid In N,N-dimethyl acetamide at 55℃; for 6h; | 84% |
3-oxo-4-(2,4,5-trifluorophenyl)-butyric acid ethyl ester
3-trifluoromethyl-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazine
1-(3-(trifluoromethyl)-5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl)-4-(2,4,5-trifluorophenyl)butane-1,3-dione
Conditions | Yield |
---|---|
With potassium tert-butylate In tetrahydrofuran at 20℃; for 1h; Reagent/catalyst; Solvent; Temperature; | 82% |
cycl-isopropylidene malonate
3-(trifluoromethyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazine hydrochloride
1-(3-(trifluoromethyl)-5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl)-4-(2,4,5-trifluorophenyl)butane-1,3-dione
Conditions | Yield |
---|---|
Stage #1: 2-(2,3,4-trifluorophenyl)acetic acid With 1,1'-carbonyldiimidazole In Isopropyl acetate at 45℃; for 0.166667h; Stage #2: cycl-isopropylidene malonate In Isopropyl acetate at 20 - 40℃; for 25.5h; Stage #3: 3-(trifluoromethyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazine hydrochloride In Isopropyl acetate at 90℃; for 12h; | 71% |
Stage #1: 2-(2,3,4-trifluorophenyl)acetic acid With 1,1'-carbonyldiimidazole In ISOPROPYLAMIDE at 45℃; for 0.166667h; Stage #2: cycl-isopropylidene malonate In ISOPROPYLAMIDE at 20 - 50℃; for 25h; Stage #3: 3-(trifluoromethyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazine hydrochloride In ISOPROPYLAMIDE at 90℃; for 12h; | 69% |
3-(trifluoromethyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazine hydrochloride
1-(3-(trifluoromethyl)-5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl)-4-(2,4,5-trifluorophenyl)butane-1,3-dione
Conditions | Yield |
---|---|
Multi-step reaction with 2 steps 1.1: potassium carbonate / toluene / 3 h / 92 - 95 °C 2.1: magnesium / tetrahydrofuran / 2.17 h / 35 - 45 °C 2.2: 4 h / 0 - 5 °C View Scheme |
3-(trifluoromethyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazine hydrochloride
1-(3-(trifluoromethyl)-5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl)-4-(2,4,5-trifluorophenyl)butane-1,3-dione
Conditions | Yield |
---|---|
Stage #1: C15H13F3O4; 3-(trifluoromethyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazine hydrochloride In N,N-dimethyl acetamide at 40 - 70℃; for 1h; Stage #2: With sodium hydrogencarbonate In N,N-dimethyl acetamide; water at 20 - 45℃; for 3 - 5h; |
sodium 1-(2,2-dimethyl-4,6-dioxo-1,3-dioxan-5-ylidene)-2-(2,4,5-trifluorophenyl)ethanolate
3-(trifluoromethyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazine hydrochloride
1-(3-(trifluoromethyl)-5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl)-4-(2,4,5-trifluorophenyl)butane-1,3-dione
Conditions | Yield |
---|---|
With methanesulfonic acid In acetonitrile at 25 - 85℃; Product distribution / selectivity; |
1-(3-(trifluoromethyl)-5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl)-4-(2,4,5-trifluorophenyl)butane-1,3-dione
Conditions | Yield |
---|---|
With potassium dichromate; sulfuric acid; acetic acid at 25 - 30℃; for 24h; |
5-(1-hydroxy-2-(2,4,5-trifluorophenyl)ethylidene)-2,2-dimethyl-1,3-dioxane-4,6-dione
1-(3-(trifluoromethyl)-5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl)-4-(2,4,5-trifluorophenyl)butane-1,3-dione
Conditions | Yield |
---|---|
With N-ethyl-N,N-diisopropylamine In toluene at 25 - 30℃; Reflux; | |
With N-ethyl-N,N-diisopropylamine In toluene at 25 - 30℃; for 8h; Product distribution / selectivity; Reflux; | |
Stage #1: 3-(trifluoromethyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-α]pyrazine hydrochloride With 4-methyl-morpholine In ethyl acetate at 10℃; for 20h; Stage #2: 5-(1-hydroxy-2-(2,4,5-trifluorophenyl)ethylidene)-2,2-dimethyl-1,3-dioxane-4,6-dione In ethyl acetate for 6h; Reflux; | 115 g |
(2,4,5-trifluorophenyl)acetic acid
1-(3-(trifluoromethyl)-5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl)-4-(2,4,5-trifluorophenyl)butane-1,3-dione
Conditions | Yield |
---|---|
Multi-step reaction with 2 steps 1.1: dmap / acetonitrile / 25 - 30 °C 1.2: 30 - 50 °C 2.1: hydrogenchloride / ethyl acetate; water / 0.5 h / 25 - 30 °C View Scheme | |
Multi-step reaction with 3 steps 1.1: oxalyl dichloride / dichloromethane; N,N-dimethyl-formamide / 4 h / 20 - 25 °C 2.1: dichloromethane / 4 h / -5 - 30 °C / Inert atmosphere 2.2: 0 - 5 °C 3.1: N-ethyl-N,N-diisopropylamine / toluene / 8 h / 25 - 30 °C / Reflux View Scheme | |
Multi-step reaction with 2 steps 1.1: dmap; pivaloyl chloride; N-ethyl-N,N-diisopropylamine / ISOPROPYLAMIDE / 2 - 3 h / 0 - 40 °C 2.1: ISOPROPYLAMIDE / 40 - 70 °C 2.2: 20 - 45 °C View Scheme |
2-(2,4,5-trifluorophenyl)acetyl chloride
1-(3-(trifluoromethyl)-5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl)-4-(2,4,5-trifluorophenyl)butane-1,3-dione
Conditions | Yield |
---|---|
Multi-step reaction with 2 steps 1.1: dichloromethane / 4 h / -5 - 30 °C / Inert atmosphere 1.2: 0 - 5 °C 2.1: N-ethyl-N,N-diisopropylamine / toluene / 8 h / 25 - 30 °C / Reflux View Scheme |
1-(3-(trifluoromethyl)-5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl)-4-(2,4,5-trifluorophenyl)butane-1,3-dione
Conditions | Yield |
---|---|
Multi-step reaction with 2 steps 1.1: dmap / acetonitrile / 25 - 30 °C 1.2: 30 - 50 °C 2.1: hydrogenchloride / ethyl acetate; water / 0.5 h / 25 - 30 °C View Scheme |
sitagliptin
1-(3-(trifluoromethyl)-5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl)-4-(2,4,5-trifluorophenyl)butane-1,3-dione
Conditions | Yield |
---|---|
Stage #1: sitagliptin With sulfuric acid; sodium nitrite Stage #2: With potassium dichromate | |
Stage #1: sitagliptin With sulfuric acid; sodium nitrite Stage #2: With potassium dichromate |
1-bromo-2,4,5-trifluorobenzene
1-(3-(trifluoromethyl)-5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl)-4-(2,4,5-trifluorophenyl)butane-1,3-dione
Conditions | Yield |
---|---|
Multi-step reaction with 2 steps 1: copper(l) iodide; L-valine; potassium phosphate / dimethyl sulfoxide / 24 h / 90 °C / Inert atmosphere 2: potassium tert-butylate / tetrahydrofuran / 1 h / 20 °C View Scheme |
1-t-Butoxycarbonylpiperazine
1-(3-(trifluoromethyl)-5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl)-4-(2,4,5-trifluorophenyl)butane-1,3-dione
Conditions | Yield |
---|---|
Multi-step reaction with 2 steps 1.1: 1,4-dioxane / 1 h / 20 °C 1.2: 7 h / 70 °C 2.1: potassium tert-butylate / tetrahydrofuran / 1 h / 20 °C View Scheme |
1-(3-(trifluoromethyl)-5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl)-4-(2,4,5-trifluorophenyl)butane-1,3-dione
Conditions | Yield |
---|---|
Multi-step reaction with 4 steps 1: hydrogenchloride / water / 5 h / 70 °C / Inert atmosphere 2: phosphonic Acid; iodine; methanesulfonic acid / 24 h / 110 °C 3: dmap; N-ethyl-N,N-diisopropylamine; pivaloyl chloride / N,N-dimethyl acetamide / 3 h / 5 - 40 °C / Inert atmosphere 4: N,N-dimethyl acetamide / 6 h / 70 °C View Scheme |
1-(3-(trifluoromethyl)-5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl)-4-(2,4,5-trifluorophenyl)butane-1,3-dione
Conditions | Yield |
---|---|
Multi-step reaction with 3 steps 1: phosphonic Acid; iodine; methanesulfonic acid / 24 h / 110 °C 2: dmap; N-ethyl-N,N-diisopropylamine; pivaloyl chloride / N,N-dimethyl acetamide / 3 h / 5 - 40 °C / Inert atmosphere 3: N,N-dimethyl acetamide / 6 h / 70 °C View Scheme |
5-(1-hydroxy-2-(2,4,5-trifluorophenyl)ethylidene)-2,2-dimethyl-1,3-dioxane-4,6-dione
1-(3-(trifluoromethyl)-5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl)-4-(2,4,5-trifluorophenyl)butane-1,3-dione
Conditions | Yield |
---|---|
In N,N-dimethyl acetamide at 70℃; for 6h; |
2,4-dichloro-5-fluorobenzoyl chloride
1-(3-(trifluoromethyl)-5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl)-4-(2,4,5-trifluorophenyl)butane-1,3-dione
Conditions | Yield |
---|---|
Multi-step reaction with 8 steps 1: potassium fluoride; tetraphenylphosphonium bromide; 18-crown-6 ether / 1,2-dichloro-benzene / 15 h / 120 - 130 °C / Inert atmosphere 2: 1,2-dichloro-benzene / 140 °C 3: potassium fluoride / 1,2-dichloro-benzene / 7 h / 110 °C / Inert atmosphere 4: sulfuric acid; sodium chloride / water / 8 h / 20 °C / Inert atmosphere 5: hydrogenchloride / water / 5 h / 70 °C / Inert atmosphere 6: phosphonic Acid; iodine; methanesulfonic acid / 24 h / 110 °C 7: dmap; N-ethyl-N,N-diisopropylamine; pivaloyl chloride / N,N-dimethyl acetamide / 3 h / 5 - 40 °C / Inert atmosphere 8: N,N-dimethyl acetamide / 6 h / 70 °C View Scheme |
1-(3-(trifluoromethyl)-5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl)-4-(2,4,5-trifluorophenyl)butane-1,3-dione
Conditions | Yield |
---|---|
Multi-step reaction with 7 steps 1: 1,2-dichloro-benzene / 140 °C 2: potassium fluoride / 1,2-dichloro-benzene / 7 h / 110 °C / Inert atmosphere 3: sulfuric acid; sodium chloride / water / 8 h / 20 °C / Inert atmosphere 4: hydrogenchloride / water / 5 h / 70 °C / Inert atmosphere 5: phosphonic Acid; iodine; methanesulfonic acid / 24 h / 110 °C 6: dmap; N-ethyl-N,N-diisopropylamine; pivaloyl chloride / N,N-dimethyl acetamide / 3 h / 5 - 40 °C / Inert atmosphere 7: N,N-dimethyl acetamide / 6 h / 70 °C View Scheme |
1-(3-(trifluoromethyl)-5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl)-4-(2,4,5-trifluorophenyl)butane-1,3-dione
Conditions | Yield |
---|---|
Multi-step reaction with 6 steps 1: potassium fluoride / 1,2-dichloro-benzene / 7 h / 110 °C / Inert atmosphere 2: sulfuric acid; sodium chloride / water / 8 h / 20 °C / Inert atmosphere 3: hydrogenchloride / water / 5 h / 70 °C / Inert atmosphere 4: phosphonic Acid; iodine; methanesulfonic acid / 24 h / 110 °C 5: dmap; N-ethyl-N,N-diisopropylamine; pivaloyl chloride / N,N-dimethyl acetamide / 3 h / 5 - 40 °C / Inert atmosphere 6: N,N-dimethyl acetamide / 6 h / 70 °C View Scheme |
1-(3-(trifluoromethyl)-5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl)-4-(2,4,5-trifluorophenyl)butane-1,3-dione
Conditions | Yield |
---|---|
Multi-step reaction with 5 steps 1: sulfuric acid; sodium chloride / water / 8 h / 20 °C / Inert atmosphere 2: hydrogenchloride / water / 5 h / 70 °C / Inert atmosphere 3: phosphonic Acid; iodine; methanesulfonic acid / 24 h / 110 °C 4: dmap; N-ethyl-N,N-diisopropylamine; pivaloyl chloride / N,N-dimethyl acetamide / 3 h / 5 - 40 °C / Inert atmosphere 5: N,N-dimethyl acetamide / 6 h / 70 °C View Scheme |
2-(2,4,5-trifluorophenyl)acetonitrile
1-(3-(trifluoromethyl)-5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl)-4-(2,4,5-trifluorophenyl)butane-1,3-dione
Conditions | Yield |
---|---|
Multi-step reaction with 3 steps 1.1: 40 - 45 °C / Inert atmosphere 2.1: trifluoroacetic acid / dichloromethane / 10 - 30 °C 3.1: oxalyl dichloride / dichloromethane / 10 - 35 °C 3.2: 0 - 15 °C View Scheme |
1-(3-(trifluoromethyl)-5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl)-4-(2,4,5-trifluorophenyl)butane-1,3-dione
Conditions | Yield |
---|---|
Multi-step reaction with 2 steps 1.1: trifluoroacetic acid / dichloromethane / 10 - 30 °C 2.1: oxalyl dichloride / dichloromethane / 10 - 35 °C 2.2: 0 - 15 °C View Scheme |
(R)-1-phenyl-ethyl-amine
1-(3-(trifluoromethyl)-5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl)-4-(2,4,5-trifluorophenyl)butane-1,3-dione
(R,Z)-3-[(1-phenylethyl)amino]-1-{3-(trifluoromethyl)-5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl}-4-(2,4,5-trifluorophenyl)but-2-en-1-one
Conditions | Yield |
---|---|
With acetic acid In toluene at 110℃; Reflux; | 100% |
With acetic acid In isopropyl alcohol at 40℃; | 99.7% |
In acetic acid; isopropyl alcohol at 50℃; for 18h; | 95.2% |
With acetic acid for 5h; Product distribution / selectivity; Reflux; | 92.07% |
(R)-1-phenyl-ethyl-amine
1-(3-(trifluoromethyl)-5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl)-4-(2,4,5-trifluorophenyl)butane-1,3-dione
(3R)-3-[[(1R)-1-phenylethyl]amino]-1-[3-(trifluoromethyl)-6,8-dihydro-5H-[1,2,4]triazolo[4,3-a]pyrazin-7-yl]-4-(2,4,5-trifluorophenyl)butan-1-one
Conditions | Yield |
---|---|
With sodium tris(acetoxy)borohydride; trifluoroacetic acid In 1,2-dichloro-ethane at 20℃; for 5h; Reagent/catalyst; Solvent; stereoselective reaction; | 95% |
(R)-2-methylpropane-2-sulfinamide
1-(3-(trifluoromethyl)-5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl)-4-(2,4,5-trifluorophenyl)butane-1,3-dione
(R)-2-methyl-N-((R)-4-oxo-4-(3-(trifluoromethyl)-5,6-dihydro-[1,2,4] triazolo[4,3-a]pyrazin-7(8H)-yl)-1-(2,4,5-trifluorophenyl)butan-2-yl)propane-2-sulfinamide
Conditions | Yield |
---|---|
With platinum(IV) oxide; hydrogen In tetrahydrofuran at 0℃; under 4500.45 Torr; for 5h; Catalytic behavior; Temperature; Pressure; Solvent; | 93% |
1-(3-(trifluoromethyl)-5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl)-4-(2,4,5-trifluorophenyl)butane-1,3-dione
(Z)-3-amino-1-(3-(trifluoromethyl)-5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl)-4-(2,4,5-trifluorophenyl)but-2-en-1-one
Conditions | Yield |
---|---|
With ammonium hydroxide; ammonium acetate In methanol at 58℃; for 0.5h; | 92% |
With ammonium acetate In methanol at 40 - 45℃; Large scale reaction; | 82% |
With ammonia In methanol at 25 - 65℃; | 79.8% |
L-phenylglycine amide
1-(3-(trifluoromethyl)-5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl)-4-(2,4,5-trifluorophenyl)butane-1,3-dione
(2S)-2({(1Z)-3-oxo-1-(2,4,5-trifluorobenzyl)-3-[3-(trifluoromethyl)-5,6-dihydro[1,2,4]triazolo[4,3-]pyrazin-7(8H)-yl]prop-1-enyl}amino-2-phenylethanamide)
Conditions | Yield |
---|---|
With acetic acid In isopropyl alcohol at 45℃; for 10h; | 91.3% |
In acetic acid; isopropyl alcohol at 50℃; for 18h; |
1-(3-(trifluoromethyl)-5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl)-4-(2,4,5-trifluorophenyl)butane-1,3-dione
sitagliptin
Conditions | Yield |
---|---|
Stage #1: 1-(3-(trifluoromethyl)-5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl)-4-(2,4,5-trifluorophenyl)butane-1,3-dione With ammonium formate; chloro(1,5-cyclooctadiene)rhodium(I) dimer; (R)-1-[(S)-2-(di-tert-butylphosphino)ferrocenyl]ethyl-di-2-methylphenylphosphine In methanol at 55℃; for 5h; Stage #2: With hydrogen In methanol at 55℃; under 12929 Torr; for 20h; Product distribution / selectivity; | 91% |
Multi-step reaction with 3 steps 1: isopropyl alcohol; acetic acid / 18 h / 50 °C 2: sodium tetrahydroborate; acetic acid / tetrahydrofuran / 3 h / 20 °C 3: 20% palladium hydroxide-activated charcoal; hydrogen; acetic acid / methanol; water / 14 h / 50 °C / 7500.75 Torr View Scheme | |
Multi-step reaction with 3 steps 1: isopropyl alcohol; acetic acid / 18 h / 50 °C 2: sodium tetrahydroborate; formic acid / tetrahydrofuran / -30 °C 3: 20% palladium hydroxide-activated charcoal; hydrogen; acetic acid / methanol; water / 14 h / 50 °C / 7500.75 Torr View Scheme |
L-phenylglycine amide
1-(3-(trifluoromethyl)-5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl)-4-(2,4,5-trifluorophenyl)butane-1,3-dione
(2S)-2({(1R)-3-oxo-1-(2,4,5-trifluorobenzyl)-3-[3-(trifluoromethyl)-5,6-dihydro[1,2,4]triazolo[4,3-α]pyrazin-7(8H)-yl]propyl}amino)-2-phenylethanamide
Conditions | Yield |
---|---|
With sodium tris(acetoxy)borohydride; acetic acid In acetonitrile at 20℃; for 5h; Reagent/catalyst; stereoselective reaction; | 87% |
1-(3-(trifluoromethyl)-5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl)-4-(2,4,5-trifluorophenyl)butane-1,3-dione
dehydrositagliptin
Conditions | Yield |
---|---|
With ammonium acetate; ammonia In methanol; water at 55℃; for 6h; | 75% |
With ammonium acetate; ammonia In methanol; water at 0 - 45℃; | |
With ammonium acetate |
1-(3-(trifluoromethyl)-5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl)-4-(2,4,5-trifluorophenyl)butane-1,3-dione
Conditions | Yield |
---|---|
Stage #1: 1-(3-(trifluoromethyl)-5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl)-4-(2,4,5-trifluorophenyl)butane-1,3-dione With dimethylsulfide borane complex In methanol at 20℃; for 0.416667h; Stage #2: With methanesulfonyl chloride; triethylamine In tetrahydrofuran at 0 - 40℃; for 20h; Temperature; Reagent/catalyst; Solvent; | 65.5% |
N-methoxylamine hydrochloride
1-(3-(trifluoromethyl)-5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl)-4-(2,4,5-trifluorophenyl)butane-1,3-dione
3-(methoxyimino)-1-(3-(trifluoromethyl)-5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl)-4-(2,4,5-trifluorophenyl)butan-1-one
Conditions | Yield |
---|---|
With pyridine In ethanol at 20℃; for 4h; | 20% |
With pyridine In ethanol at 20℃; for 4h; | 20% |
ammonia
1-(3-(trifluoromethyl)-5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl)-4-(2,4,5-trifluorophenyl)butane-1,3-dione
dehydrositagliptin
Conditions | Yield |
---|---|
With ammonium acetate In methanol; water at 0 - 45℃; for 0.25 - 0.5h; |
1-(3-(trifluoromethyl)-5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl)-4-(2,4,5-trifluorophenyl)butane-1,3-dione
Conditions | Yield |
---|---|
Stage #1: 1-(3-(trifluoromethyl)-5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl)-4-(2,4,5-trifluorophenyl)butane-1,3-dione With sodium hydroxide In methanol; water at 25 - 30℃; Stage #2: With calcium acetate In methanol; water at 25 - 60℃; |
1-(3-(trifluoromethyl)-5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl)-4-(2,4,5-trifluorophenyl)butane-1,3-dione
(R/S)-3-hydroxy-1-(3-(trifluoromethyl)-5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl)-4-(2,4,5-trifluorophenyl)butan-1-one
Conditions | Yield |
---|---|
With sodium tetrahydroborate; acetic acid at 15℃; for 2h; Product distribution / selectivity; | |
With methanol; sodium tetrahydroborate at 0℃; for 1.5h; |
1-(3-(trifluoromethyl)-5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl)-4-(2,4,5-trifluorophenyl)butane-1,3-dione
(R)-3-hydroxy-1-[3-(trifluoromethyl)-5,6-dihydro[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl]-4-(2,4,5-trifluorophenyl)butan-1-one
Conditions | Yield |
---|---|
Stage #1: 1-(3-(trifluoromethyl)-5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl)-4-(2,4,5-trifluorophenyl)butane-1,3-dione With dimethylsulfide borane complex; (3aR)-1-methyl-3,3-diphenyl-tetrahydro-pyrrolo[1,2-c][1,3,2]oxazaborole In toluene at 0 - 5℃; for 3h; Inert atmosphere; Stage #2: With methanol In toluene | |
With β-nicotinamide adenine dinucleotide phosphate disodium salt In aq. phosphate buffer; isopropyl alcohol at 37℃; Enzymatic reaction; | n/a |
1-(3-(trifluoromethyl)-5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl)-4-(2,4,5-trifluorophenyl)butane-1,3-dione
(Z)-3-(hydroxyimino)-1-(3-(trifluoromethyl)-5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl)-4-(2,4,5-trifluorophenyl)butan-1-one
Conditions | Yield |
---|---|
With pyridine; hydroxylamine hydrochloride In ethanol at 25 - 30℃; for 2h; |
1.607 g/cm3
The (2Z)-4-Oxo-4-[3-(trifluoromethyl)-5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazine-7(8H)-yl]-1-(2,4,5-trifluorophenyl)butan-2-one with the cas number 764667-65-4. It is also called (1)1,3-butanedione, 1-[5,6-dihydro-3-(trifluoromethyl)-1,2,4-triazolo[4,3-a]pyrazin-7(8H)-yl]-4-(2,4,5-trifluorophenyl)- ; (2)1,3-butanedione, 1-[5,6-dihydro-3-(trifluoromethyl)-1,2,4-triazolo[4,3-a]pyrazin-7(8H)-yl]-4-(2,4,5-trifluorophenyl)- ; (3)(2Z)-4-Oxo-4-[3-(trifluoromethyl)-5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazine-7(8H)-yl]-1-(2,4,5-trifluorophenyl)butan-2-one
Properties of (2Z)-4-Oxo-4-[3-(trifluoromethyl)-5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazine-7(8H)-yl]-1-(2,4,5-trifluorophenyl)butan-2-one:(1)ACD/LogP: 2.42 ; (2)# of Rule of 5 Violations: 0 ; (3)ACD/LogD (pH 5.5): 1 ; (4)ACD/LogD (pH 7.4): 1 ; (5)ACD/BCF (pH 5.5): 8 ; (6)ACD/BCF (pH 7.4): 8 ; (7)ACD/KOC (pH 5.5): 149 ; (8)ACD/KOC (pH 7.4): 149 ; (9)#H bond acceptors: 6 ; (10)#H bond donors: 0 ; (11)#Freely Rotating Bonds: 4 ; (12)Polar Surface Area: 68.09 Å2 ; (13)Index of Refraction: 1.58 ; (14)Molar Refractivity: 84.117 cm3 ; (15)Molar Volume: 252.865 cm3 ; (16)Polarizability: 33.347 ×10-24cm3 ; (17)Surface Tension: 41.752 dyne/cm ; (18)Density: 1.607 g/cm3 ; (19)Flash Point: 264.598 °C ; (20)Enthalpy of Vaporization: 78.542 kJ/mol ; (21)Boiling Point: 513.902 °C at 760 mmHg ; (22)Vapour Pressure: 0 mmHg at 25°C
You can still convert the following datas into molecular structure :
1. SMILES: Fc1cc(c(F)cc1F)CC(=O)CC(=O)N3Cc2nnc(n2CC3)C(F)(F)F
2. InChI: InChI=1/C16H12F6N4O2/c17-10-6-12(19)11(18)4-8(10)3-9(27)5-14(28)25-1-2-26-13(7-25)23-24-15(26)16(20,21)22/h4,6H,1-3,5,7H2
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