-Drug Synthesis Database

【结构式】

【药物名称】

【化学名称】N-[3-Chloro-4-(10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-10-ylcarbonyl)phenyl]biphenyl-2-carboxamide

【CA登记号】180416-55-1

【分子式】C₃₂H₂₄ClN₃O₂

【分子量】518.01998

【开发单位】Wyeth Pharmaceuticals (Originator)

【药理作用】CARDIOVASCULAR DRUGS, Heart Failure Therapy, Renal Failure, Agents for, RENAL-UROLOGIC DRUGS, Treatment of Renal Diseases, Vasopressin V2 Antagonists

合成路线1 合成路线2

合成路线1

The intermediate pyrrolobenzodiazepine (IV) was prepared by alkylation of pyrrole-2-carboxaldehyde (I) with 2-nitrobenzyl bromide (II), followed by reductive cyclization of the resulting nitro aldehyde (III).

参考文献中间体

【1】 Reich, M.F.; Delos Santos, E.G.; Albright, J.D.; Dusza, J.P.; Sum, F.-W.; et al.; 5-Fluoro-2-methyl-N-[4-(5H-pyrrolo[2,1-c]-[1,4]benzodiazepin-10(11H)-ylcarbonyl)-3-chlorophenyl]benzamide (VPA-985): An orally active arginine antagonist with selectivity for V2 receptors. J Med Chem 1998, 41, 14, 2442-44.
【2】 Albright, J.D.; Venkatesan, A.M.; Dusza, J.P.; Sum, F.-W. (American Cyanamid Co.); Tricyclic benzazepine vasopressin antagonists. JP 2000510154; US 5753648; WO 9749707 .
【3】 Albright, J.D.; Venkatesan, A.M.; Dusza, J.P.; Sum, F.W. (American Cyanamid Co.); Tricyclic benzazepine vasopressin antagonists. US 5700796; WO 9749708 .
【4】 Caggiano, T.J.; Bagli, J.F.; Trybulski, E.J.; Molinari, A.J.; Ashwell, M.A. (American Home Products Corp.); 3-Carboxamide derivs. of 5H-pyrrolo[1,2-c][1,4]-benzodiazepines. US 5880122 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(I)	21081	Pyrrole-2-carbaldehyde; 1H-pyrrole-2-carbaldehyde	1003-29-8	C₅H₅NO	详情	详情
(II)	21082	1-(bromomethyl)-2-nitrobenzene；2-Nitrobenzyl bromide;alpha-Bromo-2-nitrotoluene	3958-60-9	C₇H₆BrNO₂	详情	详情
(III)	21083	1-(2-nitrobenzyl)-1H-pyrrole-2-carbaldehyde; N-(2-Nitrobenzyl)pyrrole-2-carboxaldehyde	22162-51-2	C₁₂H₁₀N₂O₃	详情	详情
(IV)	21084	10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine	22162-53-4	C₁₂H₁₂N₂	详情	详情

合成路线2

Acid chloride (VI) prepared from 2-biphenylcarboxylic acid (V) and SOCl2 was coupled with methyl 4-amino-2-chlorobenzoate (VII) to yield amide (VIII). After hydrolysis of the ester group of (VIII) with NaOH, the resulting carboxylic acid (IX) was converted to acid chloride (X) using SOCl2. Finally, condensation of (X) with the tricyclic amine (IV) in the presence of DIEA furnished the title compound.

参考文献中间体

【1】 Albright, J.D.; Venkatesan, A.M.; Dusza, J.P.; Sum, F.W. (American Cyanamid Co.); Tricyclic benzazepine vasopressin antagonists. US 5700796; WO 9749708 .
【2】 Albright, J.D.; Venkatesan, A.M.; Dusza, J.P.; Sum, F.-W. (American Cyanamid Co.); Tricyclic benzazepine vasopressin antagonists. JP 2000510154; US 5753648; WO 9749707 .
【3】 Caggiano, T.J.; Bagli, J.F.; Trybulski, E.J.; Molinari, A.J.; Ashwell, M.A. (American Home Products Corp.); 3-Carboxamide derivs. of 5H-pyrrolo[1,2-c][1,4]-benzodiazepines. US 5880122 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(IV)	21084	10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine	22162-53-4	C₁₂H₁₂N₂	详情	详情
(V)	18505	[1,1'-biphenyl]-2-carboxylic acid	947-84-2	C₁₃H₁₀O₂	详情	详情
(VI)	18506	[1,1'-biphenyl]-2-carbonyl chloride		C₁₃H₉ClO	详情	详情
(VII)	26678	methyl 4-amino-2-chlorobenzoate		C₈H₈ClNO₂	详情	详情
(VIII)	41621	methyl 4-[([1,1'-biphenyl]-2-ylcarbonyl)amino]-2-chlorobenzoate		C₂₁H₁₆ClNO₃	详情	详情
(IX)	41622	4-[([1,1'-biphenyl]-2-ylcarbonyl)amino]-2-chlorobenzoic acid		C₂₀H₁₄ClNO₃	详情	详情
(X)	41623	4-[([1,1'-biphenyl]-2-ylcarbonyl)amino]-2-chlorobenzoyl chloride		C₂₀H₁₃Cl₂NO₂	详情	详情

Extended Information

Drug NewChemical Entity Original Patent(1)