(2-chloro-4-fluorophenyl)[5H-pyrrolo[2,1-c][1,4]benzodiazepin-10(11H)-yl]methanone -Drug Synthesis Database

【结构式】

【分子编号】37997

【品名】(2-chloro-4-fluorophenyl)[5H-pyrrolo[2,1-c][1,4]benzodiazepin-10(11H)-yl]methanone

【CA登记号】

【分子式】C₁₉H₁₄ClFN₂O

【分子量】340.7841432

【元素组成】C 66.97% H 4.14% Cl 10.4% F 5.57% N 8.22% O 4.69%

与该中间体有关的原料药合成路线共 2 条

合成路线1 合成路线2

合成路线1

该中间体在本合成路线中的序号：(IV)

2-Chloro-4-fluorobenzoic acid (I) was converted to acid chloride (II) upon treatment with oxalyl chloride and a catalytic amount of DMF. Subsequent coupling of (II) with pyrrolobenzodiazepine (III) yielded the corresponding amide (IV). Then, displacement of the fluorine atom of (IV) by the sodium salt of 3-methylpyrazole (V) produced a mixture of the required compound and its regioisomer (VI), which were separated by column chromatography.

参考文献中间体

合成目标

【1】 Dusza, J.P.; Ashwell, M.A.; Caggiano, T.J.; et al.; VNA-932: First orally active, nonpeptide, vasopressin V2 receptor selective agonist. 219th ACS Natl Meet (March 26 2000, San Francisco) 2000, Abst MEDI 203.
【2】 Trybulski, E.J.; Ashwell, M.A.; Molinari, A.J.; Bagli, J.F.; Chan, P.S.; Failli, A.A.; Dusza, J.P.; Albright, J.D.; Caggiano, T.J. (American Home Products Corp.); Tricyclic vasopressin agonists. EP 1000062; WO 9906409 .

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)	10801	2-Chloro-4-fluorobenzoic acid; 4-Fluoro-2-chlorobenzoic acid	2252-51-9	C₇H₄ClFO₂	详情	详情
(II)	37996	2-chloro-4-fluorobenzoyl chloride	21900-54-9	C₇H₃Cl₂FO	详情	详情
(III)	21084	10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine	22162-53-4	C₁₂H₁₂N₂	详情	详情
(IV)	37997	(2-chloro-4-fluorophenyl)[5H-pyrrolo[2,1-c][1,4]benzodiazepin-10(11H)-yl]methanone		C₁₉H₁₄ClFN₂O	详情	详情
(V)	37998	3-methyl-1H-pyrazole	1453-58-3	C₄H₆N₂	详情	详情
(VI)	37999	[2-chloro-4-(3-methyl-1H-pyrazol-1-yl)phenyl][5H-pyrrolo[2,1-c][1,4]benzodiazepin-10(11H)-yl]methanone		C₂₃H₁₉ClN₄O	详情	详情

合成路线2

该中间体在本合成路线中的序号：(VII)

Acylation of the pyrrolobenzodiazepine (I) with 2-chloro-4-fluorobenzoyl chloride (V) prepared from the acid (VI) and oxalyl chloride and catalytic DMF with Hünig's base in dichloromethane gives the acylated pyrrolobenzodiazepine (VII). Treatment of (VII) with a solution of the sodium salt of 3-methylpyrazole (VIII) in DMF yields a 85:15 mixture of WAY-VNA-932 and its 5-methyl isomer (IX) which can be separated by column chromatography using an ethyl acetate/hexane mixture over silica gel.

参考文献中间体

合成目标

【1】 Caggiano, T.J.; WAY-VNA-932. Drugs Fut 2002, 27, 3, 248.
【2】 Trybulski, E.J.; Ashwell, M.A.; Molinari, A.J.; Bagli, J.F.; Chan, P.S.; Failli, A.A.; Dusza, J.P.; Albright, J.D.; Caggiano, T.J. (American Home Products Corp.); Tricyclic vasopressin agonists. EP 1000062; WO 9906409 .

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)	21084	10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine	22162-53-4	C₁₂H₁₂N₂	详情	详情
(V)	37996	2-chloro-4-fluorobenzoyl chloride	21900-54-9	C₇H₃Cl₂FO	详情	详情
(VI)	10801	2-Chloro-4-fluorobenzoic acid; 4-Fluoro-2-chlorobenzoic acid	2252-51-9	C₇H₄ClFO₂	详情	详情
(VII)	37997	(2-chloro-4-fluorophenyl)[5H-pyrrolo[2,1-c][1,4]benzodiazepin-10(11H)-yl]methanone		C₁₉H₁₄ClFN₂O	详情	详情
(VIII)	37998	3-methyl-1H-pyrazole	1453-58-3	C₄H₆N₂	详情	详情
(IX)	52180	[2-chloro-4-(5-methyl-1H-pyrazol-1-yl)phenyl][5H-pyrrolo[2,1-c][1,4]benzodiazepin-10(11H)-yl]methanone		C₂₃H₁₉ClN₄O	详情	详情

Extended Information