495-42-1

Basic information

• Product Name: Halostachin
• Synonyms: (1R)-1-Phenyl-2-(methylamino)ethanol;[R,(-)]-α-[(Methylamino)methyl]benzyl alcohol;Halostachin
• CAS NO: 495-42-1
• Molecular Formula: C₉H₁₃NO
• Molecular Weight: 151.20600
• Mol File: 495-42-1.mol
• Article Data: 13

Chemical Properties

• Melting Point: 43-45°
• Boiling Point: 244.1±7.0 °C(Predicted)
• Appearance: /
• Density: 1.036±0.06 g/cm3(Predicted)
• PKA: 14.03±0.20(Predicted)
• CAS DataBase Reference: Halostachin(CAS DataBase Reference)
• NIST Chemistry Reference: Halostachin(495-42-1)
• EPA Substance Registry System: Halostachin(495-42-1)

Safety Data

• Hazardous Substances Data: 495-42-1(Hazardous Substances Data)

Usage

General Description

Halostachin, also known as 11α, 17α-dihydroxy-9α, 21, 21-trimethyl-19-nor-17β-pregna-1, 4-diene-3, 20-dione, is a synthetic glucocorticoid and a derivative of the natural hormone cortisone. It is used as a pharmaceutical agent for its anti-inflammatory and immunosuppressive properties, making it useful in the treatment of conditions such as asthma, allergic reactions, and autoimmune diseases. Halostachin works by inhibiting the production of inflammatory chemicals in the body, thereby reducing symptoms of inflammation. It is available in various dosage forms, including tablets, injections, and topical preparations, and is typically prescribed by healthcare professionals for short-term use due to its potential side effects and long-term risks.

InChI:InChI=1S/C9H13NO/c1-10-7-9(11)8-5-3-2-4-6-8/h2-6,9-11H,7H2,1H3

Synthetic route

(R)-3-methyl-4-phenyl-1,3-oxazolidine-2-one (291533-24-9) → (-)-Halostachine (495-42-1)

Conditions	Yield
With potassium hydroxide In water at 50℃; for 3h;	95%
With potassium hydroxide In ethanol; water at 80℃; for 10h; Hydrolysis;

(R)-2-[(tert-butoxycarbonyl)(methyl)amino]-1-phenylethanol (291533-26-1) → (-)-Halostachine (495-42-1)

Conditions	Yield
With hydrogenchloride In diethyl ether at 25℃; for 22h; Substitution;	95%

(4R,5R)-trans-5-phenyl-4-(p-tolylsulfonyl)-2-oxazoline (131101-43-4) → (-)-Halostachine (495-42-1)

Conditions	Yield
With lithium aluminium tetrahydride In tetrahydrofuran Ambient temperature;	90%
With lithium aluminium tetrahydride In tetrahydrofuran Product distribution; Ambient temperature; further reactions of other 5-alkyl-4-tosyl-2-oxazolines;	90%

2-(methylamino)-1-phenylethanol (68579-60-2) → (-)-Halostachine (495-42-1)

Conditions	Yield
With L-Tartaric acid
Multi-step reaction with 2 steps 1: 36 percent / CH2Cl2 / 0.5 h / 20 °C 2: 95 percent / KOH / H2O / 3 h / 50 °C View Scheme

N-methylamide of D-(-)-mandelic acid (2019-72-9, 65645-88-7, 89843-35-6, 96392-41-5) → (-)-Halostachine (495-42-1)

Conditions	Yield
With lithium aluminium tetrahydride

(R)-(+)-<(2-methoxy-iso-propyl)oxy>benzeneacetonitrile (142429-13-8) + methylamine (74-89-5) → (-)-Halostachine (495-42-1)

Conditions	Yield
Yield given. Multistep reaction;

N-((R)-2-Hydroxy-2-phenyl-ethyl)-formamide → N-methyl (S)-2-hydroxy-2-phenylethylamine (65058-52-8) + (-)-Halostachine (495-42-1)

Conditions	Yield
With lithium aluminium tetrahydride In diethyl ether at -10 - 20℃; for 2h; Yield given. Yields of byproduct given. Title compound not separated from byproducts;

(R)-2-[(benzoyl)(methyl)amino]-1-phenylethanol → (-)-Halostachine (495-42-1)

Conditions	Yield
With potassium hydroxide In ethanol; water at 80℃; for 8h; Substitution;

(R)-Styrene oxide (20780-53-4) + methylamine (74-89-5) → (-)-Halostachine (495-42-1)

Conditions	Yield
In methanol Heating;

2-(methylamino)-1-phenylethanone hydrochloride (23826-47-3) → N-methyl (S)-2-hydroxy-2-phenylethylamine (65058-52-8) + (-)-Halostachine (495-42-1)

Conditions	Yield
With hydrogen; potassium carbonate; [Rh((S)-binapine)(cod)]*BF4 In methanol at 50℃; under 38002.6 Torr; for 12h; Title compound not separated from byproducts.;

N-methyl-N-(2-oxo-2-phenylethyl)benzamide (42205-87-8) → (-)-Halostachine (495-42-1)

Conditions	Yield
Multi-step reaction with 2 steps 1: 96 percent / trans-RuCl2[(R)-xylbinap][(R)-daipen]; t-BuOK; H2 / propan-2-ol; 2-methyl-propan-2-ol / 12 h / 25 °C / 6080.41 Torr 2: KOH / ethanol; H2O / 8 h / 80 °C View Scheme

2-[(methoxycarbonyl)(methyl)amino]acetophenone (28126-02-5) → (-)-Halostachine (495-42-1)

Conditions	Yield
Multi-step reaction with 2 steps 1: 98 percent / trans-RuCl2[(R)-xylbinap][(R)-daipen]; t-BuOK; H2 / propan-2-ol; 2-methyl-propan-2-ol / 14 h / 25 °C / 6080.41 Torr 2: KOH / H2O; ethanol / 10 h / 80 °C View Scheme

1,1-dimethylethyl methyl(2-phenyl-2-oxoethyl)carbamate (77184-10-2) → (-)-Halostachine (495-42-1)

Conditions	Yield
Multi-step reaction with 2 steps 1: 94 percent / trans-RuCl2[(R)-xylbinap][(R)-daipen]; t-BuOK; H2 / propan-2-ol; 2-methyl-propan-2-ol / 7 h / 25 °C / 6080.41 Torr 2: 95 percent / HCl / diethyl ether / 22 h / 25 °C View Scheme

Methyl-carbamic acid (R)-2-chloro-1-phenyl-ethyl ester (913289-26-6) → (-)-Halostachine (495-42-1)

Conditions	Yield
Multi-step reaction with 2 steps 1: 96 percent / KO-t-Bu / tetrahydrofuran / 0.25 h / 20 °C 2: 95 percent / KOH / H2O / 3 h / 50 °C View Scheme

2-chloro-1-phenylethanol (56751-12-3) → (-)-Halostachine (495-42-1)

Conditions	Yield
Multi-step reaction with 3 steps 1: 89 percent / Et3N / CH2Cl2 / 20 °C 2: 96 percent / KO-t-Bu / tetrahydrofuran / 0.25 h / 20 °C 3: 95 percent / KOH / H2O / 3 h / 50 °C View Scheme

1-chloroacetophenone (532-27-4) + bis-<2-hydroxy-ethyl>-amine salt of/the/ 4-thiosemicarbazonomethyl-benzoic acid → (-)-Halostachine (495-42-1)

Conditions	Yield
Multi-step reaction with 4 steps 1: 88 percent / HCOOH; Et3N / [RuCl2(η6-p-cymene)]2; (1S,2S)-N-p-toluenesulfonyl-1,2-diphenylethylenediamine / dimethylformamide / 1.5 h / 20 °C 2: 89 percent / Et3N / CH2Cl2 / 20 °C 3: 96 percent / KO-t-Bu / tetrahydrofuran / 0.25 h / 20 °C 4: 95 percent / KOH / H2O / 3 h / 50 °C View Scheme

(R)-Mandelonitrile (10020-96-9) → (-)-Halostachine (495-42-1)

Conditions	Yield
Multi-step reaction with 3 steps 1: LiAlH4 / diethyl ether 2: diethyl ether / 1 h / -30 °C 3: LiAlH4 / diethyl ether / 2 h / -10 - 20 °C View Scheme
Multi-step reaction with 2 steps 1: 99 percent / POCl3 / 0.75 h / Ambient temperature View Scheme

(R)-2-Amino-1-phenylethanol (2549-14-6) → (-)-Halostachine (495-42-1)

Conditions	Yield
Multi-step reaction with 2 steps 1: diethyl ether / 1 h / -30 °C 2: LiAlH4 / diethyl ether / 2 h / -10 - 20 °C View Scheme

2-(N-benzyl-N-methylamino)acetophenone (33350-26-4) → (-)-Halostachine (495-42-1)

Conditions	Yield
Multi-step reaction with 2 steps 1: palladium/charcoal; ethanol / Hydrogenation 2: Lg-tartaric acid View Scheme

formaldehyd (50-00-0) + (R)-2-Amino-1-phenylethanol (2549-14-6) → (-)-Halostachine (495-42-1) + (R)-2-dimethylamino-1-phenyl-ethanol (34469-09-5)

Conditions	Yield
In formic acid at 95℃;

Glyoxal (131543-46-9) + (-)-Halostachine (495-42-1) → N-[2-hydroxy-2(R)-phenylethyl]-N-methylglycine

Conditions	Yield
With water In ethanol at 70℃; for 16h;	80%

(-)-Halostachine (495-42-1) → (R)-3-Methyl-5-phenyl-[1,2,3]oxathiazolidine 2-oxide (157586-94-2)

Conditions	Yield
With thionyl chloride; triethylamine In toluene	77%

(-)-Halostachine (495-42-1) → (5R)-2-chloro-3-methyl-5-phenyl-1,3,2-oxazaphospholidine (573987-69-6)

Conditions	Yield
With 4-methyl-morpholine; phosphorus trichloride In toluene at 0 - 20℃;	65%
With 4-methyl-morpholine; phosphorus trichloride In toluene at 0 - 20℃; Inert atmosphere;

formaldehyd (50-00-0) + formic acid (64-18-6) + (-)-Halostachine (495-42-1) → (R)-2-dimethylamino-1-phenyl-ethanol (34469-09-5)

Conditions	Yield
With water

(-)-Halostachine (495-42-1) → (R)-2-(nitroso-methyl-amino)-1-phenyl-ethanol-(1) (36972-73-3, 72656-46-3)

Conditions	Yield
With sulfuric acid; sodium nitrite

(-)-Halostachine (495-42-1) + o-<1-(trimethylsilyl)hept-6-enyl>benzaldehyde (84694-23-5) → 2-phenyl>-3-methyl-5(R)-phenyloxazolidine (84694-26-8)

Conditions	Yield
Yield given;

N-(4-chlorobenzyl)-2-(chloromethyl)-7-methyl-4-oxo-4,7-dihydrothieno[2,3-b]-pyridine-5-carboxamide (672326-01-1) + (-)-Halostachine (495-42-1) → C26H26N3O3SCl

Conditions	Yield
In N,N-dimethyl-formamide

(-)-Halostachine (495-42-1) → 5'-O-(tert-butyldiphenylsilyl)-3'-O-[(2R,5R)-3-methyl-5-phenyl-1,3,2-oxazaphospholidin-2-yl]thymidine (434937-15-2, 573987-75-4)

Conditions	Yield
Multi-step reaction with 2 steps 1: 65 percent / PCl3; 4-methylmorpholine / toluene / 0 - 20 °C 2: Et3N / tetrahydrofuran / 1 h / Heating View Scheme

(-)-Halostachine (495-42-1) → 5'-O-(tert-butyldiphenylsilyl)-3'-O-[(2S,5R)-3-methyl-5-phenyl-1,3,2-oxazaphospholidin-2-yl]thymidine

Conditions	Yield
Multi-step reaction with 2 steps 1: 65 percent / PCl3; 4-methylmorpholine / toluene / 0 - 20 °C 2: Et3N / tetrahydrofuran / 1 h / Heating View Scheme

(-)-Halostachine (495-42-1) → 5'-O-(tert-butyldiphenylsilyl)-3'-O-(3-methyl-2-oxo-5-phenyl-1,3,2-oxazaphospholidin-2-yl)thymidine

Conditions	Yield
Multi-step reaction with 3 steps 1: 65 percent / PCl3; 4-methylmorpholine / toluene / 0 - 20 °C 2: Et3N / tetrahydrofuran / 1 h / Heating 3: 100 percent / tert-butyl hydroperoxide; di-tert-butyl peroxide / acetonitrile / 0.08 h / 20 °C View Scheme

(-)-Halostachine (495-42-1) → 5'-O-[bis(4-methoxyphenyl)(phenyl)methyl]-3'-O-[(2S,5R)-3-methyl-5-phenyl-1,3,2-oxazaphospholidin-2-yl]thymidine

Conditions	Yield
Multi-step reaction with 2 steps 1: 65 percent / PCl3; 4-methylmorpholine / toluene / 0 - 20 °C 2: Et3N / tetrahydrofuran / -78 - 0 °C View Scheme

(-)-Halostachine (495-42-1) → 5'-O-[bis(4-methoxyphenyl)(phenyl)methyl]-3'-O-[(2R,5R)-3-methyl-5-phenyl-1,3,2-oxazaphospholidin-2-yl]thymidine (896723-51-6)

Conditions	Yield
Multi-step reaction with 2 steps 1: 65 percent / PCl3; 4-methylmorpholine / toluene / 0 - 20 °C 2: 818 mg / Et3N / tetrahydrofuran / -78 - 0 °C View Scheme

Upstream product

• 68579-60-2 2-(methylamino)-1-phenylethanol 
• 131101-43-4 (4R,5R)-trans-5-phenyl-4-(p-tolylsulfonyl)-2-oxazoline 
• 2019-72-9 N-methylamide of D-(-)-mandelic acid 
• 142429-13-8 (R)-(+)-<(2-methoxy-iso-propyl)oxy>benzeneacetonitrile 
• 74-89-5 methylamine 
• 291533-24-9 (R)-3-methyl-4-phenyl-1,3-oxazolidine-2-one 
• 291533-26-1 (R)-2-[(tert-butoxycarbonyl)(methyl)amino]-1-phenylethanol 
• 20780-53-4 (R)-Styrene oxide 
• 23826-47-3 2-(methylamino)-1-phenylethanone hydrochloride 
• 42205-87-8 N-methyl-N-(2-oxo-2-phenylethyl)benzamide 
• 28126-02-5 2-[(methoxycarbonyl)(methyl)amino]acetophenone 
• 77184-10-2 1,1-dimethylethyl methyl(2-phenyl-2-oxoethyl)carbamate 
• 913289-26-6 Methyl-carbamic acid (R)-2-chloro-1-phenyl-ethyl ester 
• 56751-12-3 2-chloro-1-phenylethanol 

Downstream Products

• 34469-09-5 (R)-2-dimethylamino-1-phenyl-ethanol 
• 36972-73-3 (R)-2-(nitroso-methyl-amino)-1-phenyl-ethanol-⁽¹⁾ 
• 84694-26-8 2-phenyl>-3-methyl-5(R)-phenyloxazolidine 
• 157586-94-2 (R)-3-Methyl-5-phenyl-[1,2,3]oxathiazolidine 2-oxide 
• 573987-69-6 (5R)-2-chloro-3-methyl-5-phenyl-1,3,2-oxazaphospholidine 
• 157586-95-3 (R)-3-Methyl-5-phenyl-[1,2,3]oxathiazolidine 2,2-dioxide 
• 157586-96-4 [(S)-2-(2-Methoxy-phenoxy)-2-phenyl-ethyl]-methyl-amine 
• 871937-18-7 methyl 4-(benzyloxy)-5-{[[(2R)-2-hydroxy-2-phenylethyl](methyl)amino]carbonyl}-1H-pyrazole-3-carboxylate 
• 1224582-39-1 C₃₀H₂₉ClN₄O₄ 

Relevant articles and documents

Method for synthesizing chiral alpha-amino alcohol compound

The invention discloses a method for synthesizing a chiral alpha-amino alcohol compound. The method comprises the following steps: sequentially adding an iron catalyst, a ligand, ketone, an organic solvent and silane into a reaction system at 20-30 DEG C in a nitrogen atmosphere, then stirring the obtained mixture, and carrying out column chromatography separation on the obtained product to obtain a product, namely chiral alpha-amino alcohol. According to the invention, the most high-yield iron catalyst in earth crust is used, and cheap silane (PMHS, 500 g/298 yuan) is adopted as a reducing agent, so the asymmetric reduction reaction of alpha-amino ketone can be efficiently achieved under mild conditions so as to obtain the high-yield optically-active chiral alpha-amino alcohol compound; and moreover, through the creative labor of the inventor, reaction yield can reach 99%, and meanwhile, the content of the target product in the generated reaction product is 99%.

Design and synthesis of substituted 4-oxo-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazine-2-carboxamides, novel HIV-1 integrase inhibitors

A series of 4-oxo-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazine-2-carboxamides was synthesized and tested for their inhibition of HIV-1 integrase catalytic activity and HIV-1 replication in cells. Structure-activity studies around lead compound 5 indicated that a coplanar relationship of metal-binding heteroatoms provides optimal binding to the integrase active site. Identification of potency-enhancing substituents and adjustments in lipophilicity provided 17b which inhibits integrase-catalyzed strand transfer with an IC50 value of 74 nM and inhibits HIV-1 replication in cell culture in the presence of 50% normal human serum with an IC95 value of 63 nM.

2-Aryl-2-hydroxyethylamine substituted 4-oxo-4,7-dihydrothieno[2,3-b]pyridines as broad-spectrum inhibitors of human herpesvirus polymerases

A novel series of 2-aryl-2-hydroxyethylamine substituted 4-oxo-4,7-dihydrothieno[2,3-b]pyridine-5-carboxamides have been identified as potent antivirals against human herpesviruses. These compounds demonstrate broad-spectrum inhibition of the herpesvirus polymerases HCMV, HSV-1, EBV, and VZV with high specificity compared to human DNA polymerases.