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【结 构 式】

【分子编号】21093

【品名】methyl 4-[([1,1'-biphenyl]-2-ylcarbonyl)amino]-3-methoxybenzoate

【CA登记号】

【 分 子 式 】C22H19NO4

【 分 子 量 】361.3972

【元素组成】C 73.12% H 5.3% N 3.88% O 17.71%

与该中间体有关的原料药合成路线共 1 条

合成路线1

该中间体在本合成路线中的序号:(XIII)

Title compound has been obtained by two synthetic procedures: 1) Pyrrole-2-carbaldehyde (I) was alkylated with 2-nitrobenzyl bromide (II) in the presence of NaH to afford the N-nitrobenzyl pyrrole (III). Then, reductive cyclization over Pd/C produced the pyrrolobenzodiazepine (IV). Subsequent condensation of (IV) with acid chloride (VI), prepared from 3-methoxy-4-nitrobenzoic acid (V) and oxalyl chloride, gave benzamide (VII). The nitro group of (VII) was then reduced by catalytic hydrogenation over Pd/C, and the resulting amine (VIII) was further acylated with biphenyl-2-carbonyl chloride (IX) in the presence of diisopropyl ethylamine (DIEA) to yield diamide (X). Finally, the Mannich reaction with tetramethyl diaminomethane and paraformaldehyde introduced the (dimethylamino)methyl group into the pyrrole nucleus. 2) In a related procedure, 3-methoxy-4-nitrobenzoic acid (V) was esterified with MeOH in the presence of SOCl2. The nitrobenzoic ester (XI) was reduced to aminoester (XII) by hydrogenation over Pd/C, and then acylated with biphenyl-2-carbonyl chloride (IX) and DIEA to produce amide (XIII). Subsequent saponification of the ester function of (XIII), followed by treatment with oxalyl chloride furnished acid chloride (XIV), which was then condensed with the tricyclic intermediate (IV) to yield diamide (X). Finally, the (dimethylamino)methyl group was introduced, as before, by means of a Mannich reaction.

1 Ashwell, M.A.; et al.; The design, synthesis and physicochemical properties of a novel series of human vasopressin-V2 receptor antagonists. 216th ACS Natl Meet (Aug. 23-27, Boston) 1998, Abst MEDI 061.
2 Bagli, J.F.; Ashwell, M.A.; Caggiano, T.J.; et al.; The design, synthesis and physical chemical properties of novel human vasopressin V2-receptor antagonists optimized for parenteral delivery. Bioorg Med Chem Lett 2000, 10, 8, 783.
3 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 .
4 Albright, J.D.; Venkatesan, A.M.; Dusza, J.P.; Sum, F.W. (American Cyanamid Co.); Tricyclic benzazepine vasopressin antagonists. US 5700796; WO 9749708 .
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
(V) 21085 3-methoxy-4-nitrobenzoic acid;4-Nitro-3-methoxybenzoic acid 5081-36-7 C8H7NO5 详情 详情
(VI) 21086 3-methoxy-4-nitrobenzoyl chloride C8H6ClNO4 详情 详情
(VII) 21087 (3-methoxy-4-nitrophenyl)[5H-pyrrolo[2,1-c][1,4]benzodiazepin-10(11H)-yl]methanone C20H17N3O4 详情 详情
(VIII) 21088 (4-amino-3-methoxyphenyl)[5H-pyrrolo[2,1-c][1,4]benzodiazepin-10(11H)-yl]methanone C20H19N3O2 详情 详情
(IX) 18506 [1,1'-biphenyl]-2-carbonyl chloride C13H9ClO 详情 详情
(X) 21090 N-[2-methoxy-4-[5H-pyrrolo[2,1-c][1,4]benzodiazepin-10(11H)-ylcarbonyl]phenyl][1,1'-biphenyl]-2-carboxamide C33H27N3O3 详情 详情
(XI) 21091 methyl 3-methoxy-4-nitrobenzoate 5081-37-8 C9H9NO5 详情 详情
(XII) 21092 methyl 4-amino-3-methoxybenzoate 41608-64-4 C9H11NO3 详情 详情
(XIII) 21093 methyl 4-[([1,1'-biphenyl]-2-ylcarbonyl)amino]-3-methoxybenzoate C22H19NO4 详情 详情
(XIV) 21094 4-[([1,1'-biphenyl]-2-ylcarbonyl)amino]-3-methoxybenzoyl chloride C21H16ClNO3 详情 详情
Extended Information