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【结 构 式】

【分子编号】15558

【品名】4-[[4-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)benzyl]oxy]-2-ethylquinoline; 4-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)benzyl 2-ethyl-4-quinolinyl ether

【CA登记号】

【 分 子 式 】C23H26BNO3

【 分 子 量 】375.27538

【元素组成】C 73.61% H 6.98% B 2.88% N 3.73% O 12.79%

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:(XXIV)

3) The condensation of 2-bromobenzoic acid (XII) with 4-nitroaniline (XIII) by means of SOCl2 in DMF gives the corresponding amide (XIV), which is cyclized with sodium azide and SOCl2 in acetonitrile - DMF, yielding 5-(2-bromophenyl)-1-(4-nitrophenyl)tetrazole (XV). The condensation of (XV) with the boronic acid (VI, Scheme 1) by means of Na2CO3 and tetrakis(triphenylphosphine)palladium in methanol - water - toluene affords 5-(4'-methylbiphenyl-2-yl)-1-(4-nitrophenyl)tetrazole (XVI), which is brominated with NBS and AIBN to the corresponding bromomethyl derivative (XVII). The condensation of (XVII) with quinolone (III, Scheme 1) by means of K2CO3 in hot N-methylpyrrolidone gives 2-ethyl-4-[2'-[1-(4-nitrophenyl)tetrazol-5-yl]biphenyl-4-ylmethoxy] quinoline (XVIII), which is finally deprotected with NaH and propanethiol in N-methylpyrrolidone. 4) The dehydration of the boronic acid (VI), followed by bromination with bromine and AIBN, gives 4-(bromomethyl)boronic anhydride (XIX), which is condensed with quinolone (III) by means of K2CO3 in N-methylpyrrolidone, yielding 4-(2-ethylquinolin-4-yloxymethyl)phenylboronic acid (XX). The condensation of (XX) with the bromophenyl-tetrazole (XV) by means of K2CO3 and tetrakis(triphenylphosphine)palladium in water - methanol - toluene yields compound (XVIII), already obtained (5). Scheme 2. 5) The reaction of the boronic acid (VI) with 2,2-dimethylpropane-1,3-diol (XXI) in refluxing cyclohexane gives the cyclic boronic ester (XXII), which is brominated with BBS as before to the bromomethyl derivative (XXIII). The condensation of (XXIII) with quinolone (III) affords 2-[4-(2-ethylquinolin-4-yloxymethyl)phenyl]-5,5-dimethyl-1,3,2-dioxaborinane (XXIV), which is condensed with (XV) as before to give (XVIII), already obtained.

1 Roberts, D.A.; Russell, S.T.; Pearce, R.J. (AstraZeneca plc); Quinoline derivs., process for their preparation and their use as medicaments. AU 9160955; EP 0412848; GB 2234748; JP 1991169863; US 5444071 .
2 Prous, J.; Castaner, J.; Graul, A.; ICI-D8731. Drugs Fut 1993, 18, 5, 428.
3 Bradbury, R.H.; Allott, C.P.; Dennis, M.; et al.; New nonpeptide angiotensin II receptor antagonists. 2. Synthesis, biological properties, and structure-activity relationships of 2-alkyl-4-(biphenylylmethoxy)quinoline derivatives. J Med Chem 1992, 35, 22, 4027.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(VI) 15540 4-methylphenylboronic acid; p-Tolylboronic acid 5720-05-8 C7H9BO2 详情 详情
(XII) 15546 2-bromobenzoic acid; o-bromobenzoic acid 88-65-3 C7H5BrO2 详情 详情
(XIII) 15547 4-nitrophenylamine; p-Nitroaniline; 4-nitroaniline 100-01-6 C6H6N2O2 详情 详情
(XIV) 15548 2-bromo-N-(4-nitrophenyl)benzamide C13H9BrN2O3 详情 详情
(XV) 11451 5-(2-Bromophenyl)-1-(4-nitrophenyl)-1H-1,2,3,4-tetraazole C13H8BrN5O2 详情 详情
(XVI) 15550 5-(4'-methyl[1,1'-biphenyl]-2-yl)-1-(4-nitrophenyl)-1H-1,2,3,4-tetraazole C20H15N5O2 详情 详情
(XVII) 15551 5-[4'-(bromomethyl)[1,1'-biphenyl]-2-yl]-1-(4-nitrophenyl)-1H-1,2,3,4-tetraazole C20H14BrN5O2 详情 详情
(XVIII) 15552 2-ethyl-4-quinolinyl [2'-[1-(4-nitrophenyl)-1H-1,2,3,4-tetraazol-5-yl][1,1'-biphenyl]-4-yl]methyl ether; 2-ethyl-4-([2'-[1-(4-nitrophenyl)-1H-1,2,3,4-tetraazol-5-yl][1,1'-biphenyl]-4-yl]methoxy)quinoline C20H14BrN5O2 详情 详情
(XIX) 15553 1,3-bis[4-(bromomethyl)phenyl]-3-hydroxy-1-diboroxanol C14H14B2Br2O3 详情 详情
(XX) 15554 4-[[(2-ethyl-4-quinolinyl)oxy]methyl]phenylboronic acid C18H18BNO3 详情 详情
(XXI) 12641 Neopentyl glycol; 2,2-Dimethyl-1,3-propanediol 126-30-7 C5H12O2 详情 详情
(XXII) 15556 5,5-dimethyl-2-(4-methylphenyl)-1,3,2-dioxaborinane C12H17BO2 详情 详情
(XXIII) 15557 2-[4-(bromomethyl)phenyl]-5,5-dimethyl-1,3,2-dioxaborinane C12H16BBrO2 详情 详情
(XXIV) 15558 4-[[4-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)benzyl]oxy]-2-ethylquinoline; 4-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)benzyl 2-ethyl-4-quinolinyl ether C23H26BNO3 详情 详情
Extended Information