• English
  • 简体中文
Login Register
Current Location: Home > Feedback Help Print

【结 构 式】

【分子编号】18506

【品名】[1,1'-biphenyl]-2-carbonyl chloride

【CA登记号】

【 分 子 式 】C13H9ClO

【 分 子 量 】216.66656

【元素组成】C 72.07% H 4.19% Cl 16.36% O 7.38%

与该中间体有关的原料药合成路线共 8 条

合成路线1

该中间体在本合成路线中的序号:(IX)

Alkylation of benzodiazepinone (I) with 3-(chloromethyl)- pyridine (II) in the presence of NaH gave the 1-substituted benzodiazepinone (III). Reduction of the amide group of (III) with borane in THF afforded benzodiazepine (IV). Subsequent condensation with 4-nitrobenzoyl chloride (V) gave nitrobenzamide (VI), which was reduced to amine (VII) by hydrogenation in the presence of Pd/C. This compound was coupled with acid chloride (IX) (prepared by treatment of 2-phenylbenzoic acid (VIII) with oxalyl chloride) to yield the title compound.

1 Matsuhisa, A.; Koshio, H.; Sakamoto, K.; Taniguchi, N.; Yatsu, T.; Tanaka, A.; Nonpeptide arginine vasopressin antagonists for both V1A and V2 receptors: Synthesis and pharmacological properties of 2-phenyl-4'-(2,3,4,5-tetrahydro-1H-1,5-benzodiazepine-1-carbonyl)benzanilide derivatives. Chem Pharm Bull 1998, 46, 10, 1566.
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) 18498 1,3,4,5-tetrahydro-2H-1,5-benzodiazepin-2-one C9H10N2O 详情 详情
(II) 15793 3-(Chloromethyl)pyridine 3099-31-8 C6H6ClN 详情 详情
(III) 18500 1-(3-pyridinylmethyl)-1,3,4,5-tetrahydro-2H-1,5-benzodiazepin-2-one C15H15N3O 详情 详情
(IV) 18501 1-(3-pyridinylmethyl)-2,3,4,5-tetrahydro-1H-1,5-benzodiazepine C15H17N3 详情 详情
(V) 18941 p-nitrobenzoyl chloride; 4-nitrobenzoyl chloride 122-04-3 C7H4ClNO3 详情 详情
(VI) 18503 (4-nitrophenyl)[5-(3-pyridinylmethyl)-2,3,4,5-tetrahydro-1H-1,5-benzodiazepin-1-yl]methanone C22H20N4O3 详情 详情
(VII) 18504 (4-aminophenyl)[5-(3-pyridinylmethyl)-2,3,4,5-tetrahydro-1H-1,5-benzodiazepin-1-yl]methanone C22H22N4O 详情 详情
(VIII) 18505 [1,1'-biphenyl]-2-carboxylic acid 947-84-2 C13H10O2 详情 详情
(IX) 18506 [1,1'-biphenyl]-2-carbonyl chloride C13H9ClO 详情 详情

合成路线2

该中间体在本合成路线中的序号:(XVI)

The bromination of 1-(p-toluenesulfonyl)-2,3,4,5-tetrahydro-1H-1-benzazepin-5-one (IX) with Br2 in CHCl3 gives the alpha-bromo ketone (X), which is cyclized with acetamidine hydrochloride (VIII) by means of K2CO3, yielding the expected imidazo-benzazepine (XI). This compound is detosylated with hot H2SO4 to provide 2-methyl-1,4,5,6-tetrahydroimidazo[4,5-d][1]benzazepine (XII). Acylation of (XII) with 4-nitroben-zoic acid (XIII) by means of pyridine in either hot MeCN or DMF affords the 6-(4-nitro-benzoyl) derivative (XIV), which is reduced with H2 and Raney-Ni in MeOH to the corres-ponding 6-(4-aminobenzoyl) compound (XV). Finally, this compound is condensed with biphenyl-2-carbonyl chloride (XVI) [ obtained by treatment of biphenyl-2-carboxylic acid (V) with oxalyl chloride in CH2Cl2/DMF] by means of pyridine in acetonitrile and treated with 4N HCl.

1 Castañer, R.M.; Norman, P.; Rabasseda, X.; Leeson, P.A.; Castañer, J.; Conivaptan Hydrochloride. Drugs Fut 2000, 25, 11, 1121.
2 Yamazaki, A.; Tanaka, A.; Tsunoda, T. (Yamanouchi Pharmaceutical Co., Ltd.); Novel preparation method of condensed benzazepine derivs.. JP 1996198879 .
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(V) 18505 [1,1'-biphenyl]-2-carboxylic acid 947-84-2 C13H10O2 详情 详情
(VIII) 15866 ethanimidamide C2H6N2 详情 详情
(IX) 14763 1-[(4-methylphenyl)sulfonyl]-1,2,3,4-tetrahydro-5H-1-benzazepin-5-one C17H17NO3S 详情 详情
(X) 41815 4-bromo-1-[(4-methylphenyl)sulfonyl]-1,2,3,4-tetrahydro-5H-1-benzazepin-5-one C17H16BrNO3S 详情 详情
(XI) 41816 2-methyl-6-[(4-methylphenyl)sulfonyl]-1,4,5,6-tetrahydroimidazo[4,5-d][1]benzazepine C19H19N3O2S 详情 详情
(XII) 41817 2-methyl-1,4,5,6-tetrahydroimidazo[4,5-d][1]benzazepine 318237-73-9 C12H13N3 详情 详情
(XIII) 18119 4-nitrobenzoic acid; p-nitrobenzoic acid 62-23-7 C7H5NO4 详情 详情
(XIV) 41818 [2-methyl-4,5-dihydroimidazo[4,5-d][1]benzazepin-6(1H)-yl](4-nitrophenyl)methanone C19H16N4O3 详情 详情
(XV) 41819 (4-aminophenyl)[2-methyl-4,5-dihydroimidazo[4,5-d][1]benzazepin-6(1H)-yl]methanone C19H18N4O 详情 详情
(XVI) 18506 [1,1'-biphenyl]-2-carbonyl chloride C13H9ClO 详情 详情

合成路线3

该中间体在本合成路线中的序号:(XVI)

Alternatively, treatment of biphenyl-2-carboxylic acid (V) with SOCl2 and DMF in CH2Cl2 provides the acyl chloride (XVI), which is condensed with 4-aminobenzoic acid (XVII) by means of N,N-dimethylaniline in acetone to give the corresponding 4-(2-phenylbenzamido)benzoic acid (XVIII). Treatment of (XVIII) with SOCl2 and DMF in dry THF affords the acyl chloride (XIX), which is finally condensed with the inmidazobenzazepine (XII) by means of pyridine in MeCN and treated with 4N HCl.

1 Castañer, R.M.; Norman, P.; Rabasseda, X.; Leeson, P.A.; Castañer, J.; Conivaptan Hydrochloride. Drugs Fut 2000, 25, 11, 1121.
2 Yamazaki, A.; Tanaka, A.; Tsunoda, T. (Yamanouchi Pharmaceutical Co., Ltd.); Novel preparation method of condensed benzazepine derivs.. JP 1996198879 .
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(V) 18505 [1,1'-biphenyl]-2-carboxylic acid 947-84-2 C13H10O2 详情 详情
(XII) 41817 2-methyl-1,4,5,6-tetrahydroimidazo[4,5-d][1]benzazepine 318237-73-9 C12H13N3 详情 详情
(XVI) 18506 [1,1'-biphenyl]-2-carbonyl chloride C13H9ClO 详情 详情
(XVII) 20004 p-aminobenzoic acid; 4-aminobenzoic acid 150-13-0 C7H7NO2 详情 详情
(XVIII) 41820 4-[([1,1'-biphenyl]-2-ylcarbonyl)amino]benzoic acid C20H15NO3 详情 详情
(XIX) 36810 4-[([1,1'-biphenyl]-2-ylcarbonyl)amino]benzoyl chloride C20H14ClNO2 详情 详情

合成路线4

该中间体在本合成路线中的序号:(IX)

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

合成路线5

该中间体在本合成路线中的序号:(VI)

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.

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

合成路线6

该中间体在本合成路线中的序号:(XII)

Tetrahydrobenzothiophene-4-one (I) was treated with hydroxylamine to afford oxime (IIa-b) as a mixture of syn and anti isomers, which were condensed with tosyl chloride yielding the oxime O-tosylate (IIIa-b). Beckmann rearrangement of (IIIa-b) in the presence of KOAc gave rise to lactam (IV), and subsequent reduction with borane provided thienoazepine (V). Condensation of (V) with 2-chloro-4-nitrobenzoyl chloride (VI) gave amide (VII). A 7-oxo group was introduced by oxidation of (VII) with KMnO4 in acetone-water. The resulting ketone (VIII) was treated with Bredereck’s reagent to afford the dimethylaminomethylene ketone (IX). Cyclization of (IX) with hydrazine produced the tricyclic compound (X). The nitro group of (X) was then reduced to amine (XI) using stannous chloride. Coupling of (XI) with 2-biphenylcarbonyl chloride (XII) furnished the diacylated derivative (XIII). Finally, selective monodeacylation of(XIII) with NaOH yielded the title compound.

1 Mazandarani, H.; Coupet, J.; Dusza, J.P:; Chan, P.S.; Ru, X.; Delos Santos, E.G.; Albright, J.D.; The synthesis and vasopressin (AVP) antagonist activity of a novel series of N-aroyl-2,4,5,6-tetrahydropyrazolo[3,4-d]thieno[3,2-b]azepines. Bioorg Med Chem Lett 2000, 10, 8, 695.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(IIa) 41567 (Z)-6,7-dihydro-1-benzothiophen-4(5H)-one oxime C8H9NOS 详情 详情
(IIb) 41568 (E)-6,7-dihydro-1-benzothiophen-4(5H)-one oxime C8H9NOS 详情 详情
(IIIa) 41569 (Z)-4-([[(4-methylphenyl)sulfonyl]oxy]imino)-6,7-dihydro-1-benzothiophene C15H15NO3S2 详情 详情
(IIIb) 41570 (E)-4-([[(4-methylphenyl)sulfonyl]oxy]imino)-4,5,6,7-tetrahydro-1-benzothiophene C15H15NO3S2 详情 详情
(I) 11045 6,7-Dihydro-1-benzothiophen-4(5H)-one; 4-Keto-4,5,6,7-tetrahydrothianaphthene; Tetrahydrobenzo(b)thiophene-4-one 13414-95-4 C8H8OS 详情 详情
(IV) 41571 4,6,7,8-tetrahydro-5H-thieno[3,2-b]azepin-5-one C8H9NOS 详情 详情
(V) 41572 5,6,7,8-tetrahydro-4H-thieno[3,2-b]azepine 180340-57-2 C8H11NS 详情 详情
(VI) 26674 2-chloro-4-nitrobenzoyl chloride 7073-36-1 C7H3Cl2NO3 详情 详情
(VII) 41573 (2-chloro-4-nitrophenyl)(5,6,7,8-tetrahydro-4H-thieno[3,2-b]azepin-4-yl)methanone C15H13ClN2O3S 详情 详情
(VIII) 41574 4-(2-chloro-4-nitrobenzoyl)-4,5,6,7-tetrahydro-8H-thieno[3,2-b]azepin-8-one C15H11ClN2O4S 详情 详情
(IX) 41575 4-(2-chloro-4-nitrobenzoyl)-7-[(E)-(dimethylamino)methylidene]-4,5,6,7-tetrahydro-8H-thieno[3,2-b]azepin-8-one C18H16ClN3O4S 详情 详情
(X) 41576 (2-chloro-4-nitrophenyl)[4,5-dihydropyrazolo[3,4-d]thieno[3,2-b]azepin-6(2H)-yl]methanone C16H11ClN4O3S 详情 详情
(XI) 41577 (4-amino-2-chlorophenyl)[4,5-dihydropyrazolo[3,4-d]thieno[3,2-b]azepin-6(2H)-yl]methanone C16H13ClN4OS 详情 详情
(XII) 18506 [1,1'-biphenyl]-2-carbonyl chloride C13H9ClO 详情 详情
(XIII) 41578 N-(4-[[2-([1,1'-biphenyl]-2-ylcarbonyl)-4,5-dihydropyrazolo[3,4-d]thieno[3,2-b]azepin-6(2H)-yl]carbonyl]-3-chlorophenyl)[1,1'-biphenyl]-2-carboxamide C42H29ClN4O3S 详情 详情

合成路线7

该中间体在本合成路线中的序号:(III)

 

1 MatsuhisaA,Taniguchi N,et al.2000.Nonpeptide arginine vasopressin antagonists for both VIA and V2 receptors: synthesis and pharmacological properties of 4'-(1,4,5,6-tetrahydroimidazo[4,5-d] [1] benzazepine-6-carbonyl) benzanilide derivatives and 4’-(5,6-dihydro-4H-thiazolo[5,4-d] [1] benzazepint-6-carbonyl) benzanilide derivative. Chem Pharm Bull, 48, 21~31 MatsuhisaA,Taniguchi N,et al.2000.Nonpeptide arginine vasopressin antagonists for both VIA and V2 receptors: synthesis and pharmacological properties of 4'-(1,4,5,6-tetrahydroimidazo[4,5-d] [1] benzazepine-6-carbonyl) benzanilide derivatives and 4’-(5,6-dihydro-4H-thiazolo[5,4-d] [1] benzazepint-6-carbonyl) benzanilide derivative. Chem Pharm Bull, 48, 21~31 MatsuhisaA,Taniguchi N,et al.2000.Nonpeptide arginine vasopressin antagonists for both VIA and V2 receptors: synthesis and pharmacological properties of 4'-(1,4,5,6-tetrahydroimidazo[4,5-d] [1] benzazepine-6-carbonyl) benzanilide derivatives and 4’-(5,6-dihydro-4H-thiazolo[5,4-d] [1] benzazepint-6-carbonyl) benzanilide derivative. Chem Pharm Bull, 48, 21~31
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(V) 41814 N-[4-[(4-bromo-5-oxo-2,3,4,5-tetrahydro-1H-1-benzazepin-1-yl)carbonyl]phenyl][1,1'-biphenyl]-2-carboxamide C30H23BrN2O3 详情 详情
(I) 41811 1-(4-nitrobenzoyl)-1,2,3,4-tetrahydro-5H-1-benzazepin-5-one C17H14N2O4 详情 详情
(II) 41812 1-(4-aminobenzoyl)-1,2,3,4-tetrahydro-5H-1-benzazepin-5-one C17H16N2O2 详情 详情
(III) 18506 [1,1'-biphenyl]-2-carbonyl chloride C13H9ClO 详情 详情
(IV) 41813 N-[4-[(5-oxo-2,3,4,5-tetrahydro-1H-1-benzazepin-1-yl)carbonyl]phenyl][1,1'-biphenyl]-2-carboxamide C30H24N2O3 详情 详情
(VI) 66210 N-(4-(2-methyl-1,4,5,6-tetrahydrobenzo[b]imidazo[4,5-d]azepine-6-carbonyl)phenyl)-[1,1'-biphenyl]-2-carboxamide;Conivaptan 210101-16-9 C32H26N4O2 详情 详情

合成路线8

该中间体在本合成路线中的序号:(VII)

 

1 Tsunoda T,Yamazaki A.et al.2003.vasopressin antagonist. Org Ptoc Res Dev,7 1 883~887 MatsuhisaA,Taniguchi N,et al.2000.Nonpeptide arginine vasopressin antagonists for both VIA and V2 receptors: synthesis and pharmacological properties of 4'-(1,4,5,6-tetrahydroimidazo[4,5-d] [1] benzazepine-6-carbonyl) benzanilide derivatives and 4’-(5,6-dihydro-4H-thiazolo[5,4-d] [1] benzazepint-6-carbonyl) benzanilide derivative. Chem Pharm Bull, 48, 21~31
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) 41811 1-(4-nitrobenzoyl)-1,2,3,4-tetrahydro-5H-1-benzazepin-5-one C17H14N2O4 详情 详情
(II) 66211 4-bromo-1-(4-nitrobenzoyl)-3,4-dihydro-1H-benzo[b]azepin-5(2H)-one   C17H13BrN2O4 详情 详情
(III) 41818 [2-methyl-4,5-dihydroimidazo[4,5-d][1]benzazepin-6(1H)-yl](4-nitrophenyl)methanone C19H16N4O3 详情 详情
(IV) 41819 (4-aminophenyl)[2-methyl-4,5-dihydroimidazo[4,5-d][1]benzazepin-6(1H)-yl]methanone C19H18N4O 详情 详情
(VII) 18506 [1,1'-biphenyl]-2-carbonyl chloride C13H9ClO 详情 详情
Extended Information