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【结 构 式】

【分子编号】32538

【品名】(1R)-5-bromo-1-[(1R,2S,6R,8R)-2,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.0(2,6)]dec-4-yl]-1-pentanamine; (1R)-5-bromo-1-[(1R,2S,6R,8R)-2,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.0(2,6)]dec-4-yl]pentylamine

【CA登记号】

【 分 子 式 】C15H27BBrNO2

【 分 子 量 】344.09992

【元素组成】C 52.36% H 7.91% B 3.14% Br 23.22% N 4.07% O 9.3%

与该中间体有关的原料药合成路线共 2 条

合成路线1

该中间体在本合成路线中的序号:(VII)

Coupling of 4-bromo-1-butene (I) with catecholborane (II) afforded the bromobutyl boronate (III). Subsequent exchange of (III) with alpha-pinanediol (IV) produced (V), which was regioselectively chlorinated to give (VI). Displacement of the chlorine atom of (VI) with lithium hexamethyldisilazide, followed by acid treatment furnished intermediate (VII).

1 Verbeuren, T.; Rupin, A.; De Nanteuil, G.; Gloanec, P.; New dicarbonyl cycloalkyl based thrombin inhibitors with improved activity and selectivity compared to (D)-Phe-Pro-boroArg derivatives . 218th ACS Natl Meet (Aug 22 1999, New Orleans) 1999, Abst MEDI 201.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
34273 N,N-bis(trimethylsilyl)amine; trimethyl-N-(trimethylsilyl)silanamine 999-97-3 C6H19NSi2 详情 详情
(I) 11720 4-Bromo-1-butene 5162-44-7 C4H7Br 详情 详情
(II) 32533 1,3,2-benzodioxaborole 274-07-7 C6H5BO2 详情 详情
(III) 32534 2-(4-bromobutyl)-1,3,2-benzodioxaborole C10H12BBrO2 详情 详情
(IV) 32535 (1R,2S,3R,5R)-2,6,6-trimethylbicyclo[3.1.1]heptane-2,3-diol C10H18O2 详情 详情
(V) 32536 (1R,2S,6R,8R)-4-(5-bromopentyl)-2,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.0(2,6)]decane C15H26BBrO2 详情 详情
(VI) 32537 (1R,2S,6R,8R)-4-[(1R)-5-bromo-1-chloropentyl]-2,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.0(2,6)]decane C15H25BBrClO2 详情 详情
(VII) 32538 (1R)-5-bromo-1-[(1R,2S,6R,8R)-2,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.0(2,6)]dec-4-yl]-1-pentanamine; (1R)-5-bromo-1-[(1R,2S,6R,8R)-2,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.0(2,6)]dec-4-yl]pentylamine C15H27BBrNO2 详情 详情

合成路线2

该中间体在本合成路线中的序号:(VII)

Condensation of cyclopentanecarboxylic acid (VIII) with ethyl chloroformate in the presence of LDA afforded 1,1-cyclopentanedicarboxylic acid monoethyl ester (IX), which was coupled with phenethylamine (X) by means of TBTU to produce amide (XI). Ester hydrolysis of (XI) with NaOH gave carboxylic acid (XII), which was activated as the mixed anhydride (XIII) with isobutyl chloroformate, and then coupled to the chiral aminoboronate (VII), yielding diamide (XIV). Displacement of the bromine of (XIV) with NaN3, followed by hydrogenation of the resulting azide (XV) gave rise to amine (XVI). The chiral auxiliary of (XVI) was finally removed by treatment with phenylboronic acid.

1 Verbeuren, T.; Rupin, A.; De Nanteuil, G.; Gloanec, P.; New dicarbonyl cycloalkyl based thrombin inhibitors with improved activity and selectivity compared to (D)-Phe-Pro-boroArg derivatives . 218th ACS Natl Meet (Aug 22 1999, New Orleans) 1999, Abst MEDI 201.
2 Gloanec, P.; Portevin, B.; Lila, C.; Rupin, A.; de Nanteuil, G.; Simonet, S.; Verbeuren, T. (ADIR et Cie.); Cpds. derived from boronic acid. EP 0792883; FR 2745288; US 5814622 .
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
11229 1-[(Chlorocarbonyl)oxy]ethane;ethyl carbonochloridate; Carbonchloridic acid ethyl ester;Ethyl chloroformate;Ethyl chlorocarbonate 541-41-3 C3H5ClO2 详情 详情
(VII) 32538 (1R)-5-bromo-1-[(1R,2S,6R,8R)-2,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.0(2,6)]dec-4-yl]-1-pentanamine; (1R)-5-bromo-1-[(1R,2S,6R,8R)-2,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.0(2,6)]dec-4-yl]pentylamine C15H27BBrNO2 详情 详情
(VIII) 20734 cyclopentanecarboxylic acid 3400-45-1 C6H10O2 详情 详情
(IX) 32539 1-(ethoxycarbonyl)cyclopentanecarboxylic acid C9H14O4 详情 详情
(X) 18333 Phenethylamine; 2-Phenyl-1-ethanamine 64-04-0 C8H11N 详情 详情
(XI) 32540 ethyl 1-[(phenethylamino)carbonyl]cyclopentanecarboxylate C17H23NO3 详情 详情
(XII) 32541 1-[(phenethylamino)carbonyl]cyclopentanecarboxylic acid C15H19NO3 详情 详情
(XIII) 32542 1-[N-(2-Phenylethyl)carbamoyl]cyclopentylcarbonyl isobutoxycarbonyl anhydride C20H27NO5 详情 详情
(XIV) 32543 N(1)-[(1R)-5-bromo-1-[(1R,2S,6R,8R)-2,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.0(2,6)]dec-4-yl]pentyl]-N(1)-phenethyl-1,1-cyclopentanedicarboxamide C30H44BBrN2O4 详情 详情
(XV) 32544 N(1)-[(1R)-5-azido-1-[(1R,2S,6R,8R)-2,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.0(2,6)]dec-4-yl]pentyl]-N(1)-phenethyl-1,1-cyclopentanedicarboxamide C30H44BN5O4 详情 详情
(XVI) 32545 N(1)-[(1R)-5-amino-1-[(1R,2S,6R,8R)-2,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.0(2,6)]dec-4-yl]pentyl]-N(1)-phenethyl-1,1-cyclopentanedicarboxamide C30H46BN3O4 详情 详情
Extended Information