194032-32-1

Basic information

• Product Name: (S)-1-BOC-2-METHYL-[1,4]DIAZEPANE
• Synonyms: (S)-1-BOC-2-METHYL-[1,4]DIAZEPANE;(3S)-tert-butoxyl-3-Methyl-1-carbonyl-1,4-diazepine;(3S)-Hexahydro-3-Methyl-1H-1,4-diazepine-1-carboxylic Acid 1,1-DiMethylethyl Ester;(S)-tert-butyl-3-Methyl-1,4-diazepane-1-carboxylate;(S)-Hexahydro-3-methyl-1H-1,4-Diazepine-1-carboxylic acid tert-butyl ester;(S)-tert-butoxyl-3-Methyl-1-carbonyl-1,4-diazepine;(S)-1-Boc-3-methyl-[1,4]diazepane;1H-1,4-Diazepine-1-carboxylic acid, hexahydro-3-methyl-, 1,1-dimethylethyl ester, (S)-
• CAS NO: 194032-32-1
• Molecular Formula: C₁₁H₂₂N₂O₂
• Molecular Weight: 214.3
• EINECS: 1592732-453-0
• Product Categories: Chiral Reagents
• Mol File: 194032-32-1.mol

Chemical Properties

• Boiling Point: 288℃
• Flash Point: 128℃
• Appearance: Yellow Oil
• Density: 0.980
• Storage Temp.: 2-8°C(protect from light)
• PKA: 10.42±0.40(Predicted)
• CAS DataBase Reference: (S)-1-BOC-2-METHYL-[1,4]DIAZEPANE(CAS DataBase Reference)
• NIST Chemistry Reference: (S)-1-BOC-2-METHYL-[1,4]DIAZEPANE(194032-32-1)
• EPA Substance Registry System: (S)-1-BOC-2-METHYL-[1,4]DIAZEPANE(194032-32-1)

Safety Data

• Hazardous Substances Data: 194032-32-1(Hazardous Substances Data)

Usage

Uses

Used in Organic Synthesis:
(S)-1-Boc-2-methyl-[1,4]diazepane is used as a synthetic building block for the creation of various complex organic molecules. Its unique structure and functional groups make it a valuable component in the synthesis of pharmaceuticals, agrochemicals, and other specialty chemicals.
Used in Pharmaceutical Industry:
In the pharmaceutical industry, (S)-1-Boc-2-methyl-[1,4]diazepane is used as an intermediate in the development of new drugs. Its incorporation into drug molecules can potentially enhance their pharmacological properties, such as potency, selectivity, and bioavailability.
Used in Agrochemical Industry:
(S)-1-Boc-2-methyl-[1,4]diazepane is also utilized as a key component in the synthesis of agrochemicals, such as pesticides and herbicides. Its presence in these molecules can contribute to improved efficacy and selectivity, leading to more effective and environmentally friendly products.
Used in Specialty Chemicals:
In the specialty chemicals sector, (S)-1-Boc-2-methyl-[1,4]diazepane is employed as a versatile building block for the synthesis of various high-value compounds. These compounds can be used in a wide range of applications, including materials science, coatings, and adhesives.

Synthetic route

tert-butyl (S)-3-methyl-4-[(2-nitrophenyl)sulfonyl]-1,4-diazepane-1-carboxylate (949109-36-8) → (S)-tert-butyl 3-methyl-1,4-diazepane-1-carboxylate (194032-32-1)

Conditions	Yield
With potassium carbonate; thiophenol In acetonitrile at 20℃; for 18h; Inert atmosphere; Large scale;	86%
With potassium carbonate; thiophenol In acetonitrile at 20℃; for 24h;	85.7%

(S)-1-benzyl 4-tert-butyl 2-methyl-1,4-diazepane-1,4-dicarboxylate (1360538-91-5) → (S)-tert-butyl 3-methyl-1,4-diazepane-1-carboxylate (194032-32-1)

Conditions	Yield
With palladium 10% on activated carbon; hydrogen In methanol; mineral oil at 20℃; for 19h; Inert atmosphere;	60.7%

tert-butyl (S)-4-benzyl-3-methyl-1,4-diazepane-1-carboxylate (1001401-71-3) → (S)-tert-butyl 3-methyl-1,4-diazepane-1-carboxylate (194032-32-1)

Conditions	Yield
With hydrogen; palladium dihydroxide In methanol; ethyl acetate

di-tert-butyl dicarbonate (24424-99-5) → (S)-tert-butyl 3-methyl-1,4-diazepane-1-carboxylate (194032-32-1)

Conditions	Yield
Multi-step reaction with 2 steps 1: potassium carbonate / water; ethanol / Inert atmosphere; Large scale 2: potassium carbonate; thiophenol / acetonitrile / 18 h / 20 °C / Inert atmosphere; Large scale View Scheme

(S)-tert-butyl 3-hydroxypropyl(2-(2-nitrophenylsulfonylamide)propyl)carbamate (949109-35-7) → (S)-tert-butyl 3-methyl-1,4-diazepane-1-carboxylate (194032-32-1)

Conditions	Yield
Multi-step reaction with 2 steps 1: triphenylphosphine; di-isopropyl azodicarboxylate / tetrahydrofuran / 9 h / 5 - 20 °C / Inert atmosphere; Large scale 2: potassium carbonate; thiophenol / acetonitrile / 24 h / 20 °C View Scheme

(S)-N-{1-[(3-hydroxypropyl)amino]propan-2-yl}-2-nitrobenzenesulfonamide (1360538-87-9) → (S)-tert-butyl 3-methyl-1,4-diazepane-1-carboxylate (194032-32-1)

Conditions	Yield
Multi-step reaction with 4 steps 1: triphenylphosphine; di-isopropyl azodicarboxylate / tetrahydrofuran / 16 h / 5 - 20 °C / Inert atmosphere 2: hydrogenchloride / water; ethyl acetate / pH 4 / Large scale 3: potassium carbonate / water; ethanol / 5 h / 5 °C / Large scale 4: potassium carbonate; thiophenol / acetonitrile / 24 h / 20 °C View Scheme

4-fluoroisoquinoline-5-sulfonyl chloride hydrochloride (906820-08-4) + (S)-tert-butyl 3-methyl-1,4-diazepane-1-carboxylate (194032-32-1) → (S)-tert-butyl 4-[(4-fluoroisoquinoline-5-yl)sulfonyl]-3-methyl-1,4-diazepane-1-carboxylate (1360538-86-8)

Conditions	Yield
With triethylamine In acetonitrile for 2h; Solvent; Time; Temperature; Inert atmosphere; Cooling with ice; Large scale;	100%

4-fluoroisoquinoline-5-sulfonyl chloride hydrochloride (906820-08-4) + (S)-tert-butyl 3-methyl-1,4-diazepane-1-carboxylate (194032-32-1) → 4-fluoro-5-[[(2S)-hexahydro-2-methyl-1H-1,4-diazepin-1-yl]sulfonyl]isoquinoline hydrochloride (223644-02-8)

Conditions	Yield
With triethylamine In tetrahydrofuran at 0℃; for 2h;	97%

2-(2H-1,2,3-triazol-2-yl)benzoic acid (1001401-62-2) + (S)-tert-butyl 3-methyl-1,4-diazepane-1-carboxylate (194032-32-1) → tert-butyl (S)-3-methyl-4-(2-(2H-1,2,3-triazol-2-yl)benzoyl)-1,4-diazepane-1-carboxylate (1001401-72-4)

Conditions	Yield
With benzotriazol-1-ol; N-(3-dimethylaminopropyl)-N-ethylcarbodiimide; triethylamine In N,N-dimethyl-formamide at 50℃;

Upstream product

• 24424-99-5 di-tert-butyl dicarbonate 
• 949109-36-8 tert-butyl (S)-3-methyl-4-[(2-nitrophenyl)sulfonyl]-1,4-diazepane-1-carboxylate 
• 1360538-91-5 (S)-1-benzyl 4-tert-butyl 2-methyl-1,4-diazepane-1,4-dicarboxylate 
• 1360538-90-4 (S)-6-benzyloxycarbonylamino-4-(tert-butoxycarbonyl)-4-azaheptyl methanesulfonate 
• 913625-37-3 (S)-6-benzyloxycarbonylamino-4-(tert-butoxycarbonyl)-4-azaheptan-1-ol 
• 1360538-89-1 (S)-2-methyl-1-[(2-nitrophenyl)sulfonyl]-1,4-diazepane 
• 1360538-87-9 (S)-N-{1-[(3-hydroxypropyl)amino]propan-2-yl}-2-nitrobenzenesulfonamide 
• 949109-35-7 (S)-tert-butyl 3-hydroxypropyl(2-(2-nitrophenylsulfonylamide)propyl)carbamate 
• 1001401-71-3 tert-butyl (S)-4-benzyl-3-methyl-1,4-diazepane-1-carboxylate 

Downstream Products

• 1001401-72-4 tert-butyl (S)-3-methyl-4-(2-(2H-1,2,3-triazol-2-yl)benzoyl)-1,4-diazepane-1-carboxylate 
• 223645-67-8 ripasudil 
• 223644-02-8 4-fluoro-5-[[(2S)-hexahydro-2-methyl-1H-1,4-diazepin-1-yl]sulfonyl]isoquinoline hydrochloride 

Relevant articles and documents

MANUFACTURING METHOD OF OPTICALLY ACTIVE CARBINOL COMPOUND

PROBLEM TO BE SOLVED: To provide a manufacturing method of an optically active carbinol compound having LXRβ activation action and a manufacturing intermediate thereof. SOLUTION: A manufacturing method of an optically active compound represented by the formula (1) comprises manufacturing a 2-(4-(2,5-dimethylpiperazin-1-yl)-3-propylphenyl)-1,1,1,3,3,3-hexafluoropropan-2-ol compound which is an important optically active intermediate. COPYRIGHT: (C)2015,JPOandINPIT

NOVEL PRODUCTION METHOD FOR ISOQUINOLINE DERIVATIVES AND SALTS THEREOF

The present invention provides a method capable of industrially producing a target product, i.e., a compound represented by the aforementioned formula (I) or a salt thereof, which is useful for preventing and treating cerebrovascular disorders such as cerebral infarction, cerebral hemorrhage, subarachnoid hemorrhage, and cerebral edema, particularly for preventing and treating glaucoma, at high yield even on a large scale without imposing a negative impact on the environment. The present invention provides a method for producing a compound represented by formula (I) or a salt thereof, wherein the method comprises a step of reacting a compound represented by formula (III) or a salt thereof with a compound represented by formula (II) in the presence of at least one solvent selected from the group consisting of a nitrile solvent, an amide solvent, a sulfoxide solvent, and a urea solvent, and a base.

A practical synthesis of (S)- tert -butyl 3-methyl-1,4-diazepane-1- carboxylate, the key intermediate of rho-kinase inhibitor K-115

A practical synthesis of (S)-tert-butyl 3-methyl-1,4-diazepane-1- carboxylate has been established for supplying this key intermediate of Rho-kinase inhibitor K-115 in a multikilogram production. The chiral 1,4-diazepane was constructed by intramolecular Fukuyama-Mitsunobu cyclization of a N-nosyl diamino alcohol starting from the commercially available (S)- or (R)-2-aminopropan-1-ol. In the same manner, an enantiomeric pair of a structural isomer were prepared for demonstration of the synthetic utility.

SUBSTITUTED DIAZEPAN OREXIN RECEPTOR ANTAGONISTS

The present invention is directed to substituted diazepan compounds which are antagonists of orexin receptors, and which are useful in the treatment or prevention of neurological and psychiatric disorders and diseases in which orexin receptors are involved. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which orexin receptors are involved.