127061-43-2

Basic information

• Product Name: (3R,4S)-3-hydroxy-4-(4-methoxyphenyl)-6-(trifluoromethyl)-1,3,4,5-tetrahydro-2H-1-benzazepin-2-one
• CAS NO: 127061-43-2
• Molecular Formula: C₁₈H₁₆F₃NO₃
• Molecular Weight: 351.3197
• Mol File: 127061-43-2.mol
• Article Data: 5

Chemical Properties

• Boiling Point: 482.1°C at 760 mmHg
• Flash Point: 245.4°C
• Density: 1.324g/cm³
• Vapor Pressure: 4.17E-10mmHg at 25°C
• Refractive Index: 1.547
• CAS DataBase Reference: (3R,4S)-3-hydroxy-4-(4-methoxyphenyl)-6-(trifluoromethyl)-1,3,4,5-tetrahydro-2H-1-benzazepin-2-one(CAS DataBase Reference)
• NIST Chemistry Reference: (3R,4S)-3-hydroxy-4-(4-methoxyphenyl)-6-(trifluoromethyl)-1,3,4,5-tetrahydro-2H-1-benzazepin-2-one(127061-43-2)
• EPA Substance Registry System: (3R,4S)-3-hydroxy-4-(4-methoxyphenyl)-6-(trifluoromethyl)-1,3,4,5-tetrahydro-2H-1-benzazepin-2-one(127061-43-2)

Safety Data

• Hazardous Substances Data: 127061-43-2(Hazardous Substances Data)

Upstream product

• 126958-69-8 4,5-Dihydro-4-(4-methoxyphenyl)-6-(trifluoromethyl)-1H-1-benzazepine-2,3-dione 
• 127061-41-0 (cis)-3-[(2-Carboxybenzoyl)oxy]-1,3,4,5-tetrahydro-4-(4-methoxyphenyl)-6-(trifluoromethyl)-2H-1-benzazepin-2-one 
• 138337-24-3 6-(trifluoromethyl)-1,3,4,5-tetrahydro-3-hydroxy-3-(methoxycarbonyl)-4-(4-methoxyphenyl)-2H-1-benzazepin-2-one 
• 111604-99-0 [1-(4-Methoxyphenyl)-2-[2-nitro-6-(trifluoromethyl)phenyl]ethyl]propanedioic acid,dimethyl ester 
• 138383-10-5 1,3,4,5-tetrahydro-6-(trifluoromethyl)-3-(methoxycarbonyl)-4-(4-methoxyphenyl)-2H-1-benzazepin-2-one 
• 111605-05-1 [2-(2-amino-6-trifluoromethylphenyl)-1-(4-methoxyphenyl)ethyl]propanedioic acid,dimethyl ester 
• 7443-25-6 dimethyl 2-(4-methoxybenzylidene)malonate 
• 6656-49-1 2-methyl-1-nitro-3-(trifluoromethyl)benzene 
• 138337-24-3 (3R,4R)-3-Hydroxy-4-(4-methoxy-phenyl)-2-oxo-6-trifluoromethyl-2,3,4,5-tetrahydro-1H-benzo[b]azepine-3-carboxylic acid methyl ester 
• 111605-09-5 (3S,4S-trans)-1,3,4,5-tetrahydro-6-(trifluoromethyl)-3-(methoxycarbonyl)-4-(4-methoxyphenyl)-2H-1-benzazepin-2-one 
• 111688-58-5 (3S,4S-trans)-3-carboxy-1,3,4,5-tetrahydro-4-(4-methoxyphenyl)-6-(trifluoromethyl)-2H-1-benzazepin-2-one (S)-α-methylbenzylamine salt 
• 133963-42-5 (3R,4S)-3-Hydroxy-4-(4-methoxy-phenyl)-6-trifluoromethyl-1,3,4,5-tetrahydro-benzo[b]azepin-2-one 
• 138337-24-3 (3S,4S)-1,3,4,5-tetrahydro-6-(trifluoromethyl)-3-hydroxy-3-(methoxycarbonyl)-4-(4-methoxyphenyl)-2H-1-benzazepin-2-one 

Downstream Products

• 138384-10-8 (3R,4S)-3-Hydroxy-4-(4-methoxy-phenyl)-1-[2-(tetrahydro-pyran-2-yloxy)-ethyl]-6-trifluoromethyl-1,3,4,5-tetrahydro-benzo[b]azepin-2-one 
• 128510-26-9 <3R-<1(S^*),3α,4α>>-3-(acetyloxy)-1-<<(benzyloxycarbonyl)-2-pyrrolidinyl>methyl>-1,3,4,5-tetrahydro-4-(4-methoxyphenyl)-6-(trifluoromethyl)-2H-1-benzazepin-2-one 
• 133963-43-6 [3R-(1(S^*),3α,4α)]-3-(acetyloxy)-1,3,4,5-tetrahydro-4-(4-methoxyphenyl)-1-(2-pyrrolidinylmethyl)-6-(trifluoromethyl)-2H-1-benzazepin-2-one 
• 138383-16-1 (3R,4S-cis)-1,3,4,5-tetrahydro-6-(trifluoromethyl)-3-hydroxy-1-<2-(dimethylamino)ethyl>-4-(4-methoxyphenyl)-2H-1-benzazepin-2-one monohydrochloride 
• 127061-41-0 (cis)-3-[(2-Carboxybenzoyl)oxy]-1,3,4,5-tetrahydro-4-(4-methoxyphenyl)-6-(trifluoromethyl)-2H-1-benzazepin-2-one 
• 128573-84-2 Acetic acid (3R,4S)-4-(4-methoxy-phenyl)-1-((R)-1-methyl-pyrrolidin-2-ylmethyl)-2-oxo-6-trifluoromethyl-2,3,4,5-tetrahydro-1H-benzo[b]azepin-3-yl ester 
• 128704-84-7 <3R-<1(S^*),3α,4α>>-3-(acetyloxy)-1-<(1-methyl-2-pyrrolidinyl)methyl>-1,3,4,5-tetrahydro-4-(4-methoxyphenyl)-6-(trifluoromethyl)-2H-1-benzazepin-2-one 
• 131614-47-6 Acetic acid (3R,4S)-4-(4-methoxy-phenyl)-2-oxo-1-(R)-1-pyrrolidin-2-ylmethyl-6-trifluoromethyl-2,3,4,5-tetrahydro-1H-benzo[b]azepin-3-yl ester 
• 128573-91-1 (3R,4S)-3-Hydroxy-4-(4-methoxy-phenyl)-1-(R)-1-pyrrolidin-2-ylmethyl-6-trifluoromethyl-1,3,4,5-tetrahydro-benzo[b]azepin-2-one 
• 128510-26-9 (R)-2-[(3R,4S)-3-Acetoxy-4-(4-methoxy-phenyl)-2-oxo-6-trifluoromethyl-2,3,4,5-tetrahydro-benzo[b]azepin-1-ylmethyl]-pyrrolidine-1-carboxylic acid benzyl ester 
• 138840-02-5 Acetic acid (3R,4S)-4-(4-methoxy-phenyl)-2-oxo-1-[2-(tetrahydro-pyran-2-yloxy)-ethyl]-6-trifluoromethyl-2,3,4,5-tetrahydro-1H-benzo[b]azepin-3-yl ester 
• 138353-60-3 (3R,4S-cis)-1-(carboxymethyl)-1,3,4,5-tetrahydro-6-(trifluoromethyl)-3-acetoxy-4-(4-methoxyphenyl)-2H-1-benzazepin-2-one 
• 138353-59-0 (3R,4S-cis)-1,3,4,5-tetrahydro-6-(trifluoromethyl)-3-acetoxy-1-(2-hydroxyethyl)-4-(4-methoxyphenyl)-2H-1-benzazepin-2-one 
• 138353-58-9 (3R,4S-cis)-1-(formylmethyl)-1,3,4,5-tetrahydro-6-(trifluoromethyl)-3-acetoxy-4-(4-methoxyphenyl)-2H-1-benzazepin-2-one 

Relevant articles and documents

Chemoenzymatic synthesis of benzazepinone calcium channel blocking agents

The synthesis of a 6-trifluoromethyl-benzazepin-2-one derivative (3) from readily available nitro-toluene (4) is described.This synthetic route requires an enantio- and stereo-selective microbial reduction of racemic 13 to form (3R,4S)-cis-alcohol (10).Compound 3 is potent calcium channel blocking agent both in vitro and in vivo.

Benzazepinone calcium channel blockers. 2. Structure-activity and drug metabolism studies leading to potent antihypertensive agents. Comparison with benzothiazepinones

As part of a program to discover potent antihypertensive analogues of diltiazem (3a), we prepared 1-benzazepin-2-ones (4). Benzazepinones competitively displace radiolabeled diltiazem, and show the same absolute stereochemical preferences at the calcium channel receptor protein. Derivatives of 4 containing a trifluoromethyl substituent in the fused aromatic ring show potent and long-acting antihypertensive activity. Studies of the metabolism of 4 lead to the metabolically stable antihypertensive calcium channel blockers 5a and 5c. Benzazepinone 5a is a longer acting and more potent antihypertensive agent than the second generation diltiazem analogue TA-3090 (3e).

Resolution process for benzazepine intermediates

In accordance with the present invention an improved process for preparing resolved compounds of the formula STR1 being the cis(+) isomer, is disclosed, wherein R1 and R2 are each independently hydrogen, halogen, alkyl, alkoxy, aryloxy, arylalkoxy, diarylalkoxy, arylalkyl, cyano, hydroxy, alkanoyloxy, STR2 fluoro substituted alkoxy, fluoro substituted alkyl, (cycloalkyl)alkoxy --NO2, NX3 X4, --S(O)m alkyl, STR3 m is 0, 1 or 2; X1 and X2 are each independently hydrogen, alkyl, aryl or heteroaryl, or X1 and X2 together with the nitrogen atom to which they are attached are pyrrolidinyl, piperidinyl or morpholinyl; X3 and X4 are each independently hydrogen, alkyl, alkanoyl, arylcarbonyl, heteroarylcarbonyl, or STR4 X5 is hydroxy, alkoxy, aryloxy, amino, alkylamino or dialkylamino; and X6 is alkyl, alkoxy or aryloxy; with the proviso that if R4 is a 7-alkyl group, it must have a tertiary carbon atom bonded to the ring.