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【结 构 式】

【分子编号】65758

【品名】 

【CA登记号】 

【 分 子 式 】C21H26F3N3O5S3

【 分 子 量 】553.6478696

【元素组成】C 45.56% H 4.73% F 10.29% N 7.59% O 14.45% S 17.38%

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:(VIII)

Ring opening of 3(R)-(benzyloxycarbonylamino)-γ-butyrolactone (I) with morpholine (II) in dioxane at 65 °C provides the morpholide (III), which is condensed with diphenyl disulfide in the presence of Bu3P in hot toluene, yielding the phenyl thioether (IV). Then, the benzyloxycarbonyl protecting group is removed with 30% HBr in AcOH, and the resulting deprotected amino-amide (V) is reduced to diamine (VI) using a solution of borane in tetrahydrofuran (1). Subsequent coupling of diamine (VI) with 4-fluoro-3-(trifluoromethylsulfonyl)benzenesulfonamide (VII) in the presence of DIEA in THF or DMSO gives the sulfanilamide (VIII) (1-3), which is finally acylated with the piperazinylbenzoic acid derivative (IX) by means of EDC and DMAP in CH2Cl 2 (1-4). Scheme 1.

1 Bruncko, M., Ding, H., Elmore, S.W. et al. (Abbott Laboratories Inc.). Apoptosis promoters. EP 1888550, US 2007027135, US 7390799, WO 2007040650.
2 Ding, H., Park, C.-M., Bruncko, M. et al. ABT-263, an orally bioavailable inhibitor of Bcl-2 family proteins. 235th ACS Natl Meet (April 6-10, New Orleans) 2008, Abst MEDI 110.
3 Zhang, H., Zhou, J., Ha, C., Pei, D., Ding, K. An efficient synthesis of ABT-263, a novel inhibitor of antiapoptotic Bcl-2 proteins. Synthesis 2008, (15): 2398-404.
4 Song, X., Bruncko, M., Ding, H. et al. P2 site SAR development toward ABT-263, an orally bioavailable inhibitor of Bcl-2 family proteins. 235th ACS Natl Meet (April 6-10, New Orleans) 2008, Abst MEDI 78.
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) 65752 3(R )-(benzyloxycarbonylamino)-γ-butyrolactone; Benzyl (R)-5-oxotetrahydrofuran-3-ylcarbamate; N-[(3R)-Tetrahydro-5-oxo-3-furanyl]carbamic acid phenylmethyl ester 118399-28-3 C12H13NO4 详情 详情
(II) 10388 Morpholine 110-91-8 C4H9NO 详情 详情
(III) 65753     C16H22N2O5 详情 详情
(IV) 65754     C22H26N2O4S 详情 详情
(V) 65755     C14H20N2O2S 详情 详情
(VI) 65756     C14H22N2OS 详情 详情
(VII) 65757 4-Fluoro-3-(trifluoromethylsulfonyl)benzenesulfonamide 1027345-08-9 C7H5F4NO4S2 详情 详情
(VIII) 65758     C21H26F3N3O5S3 详情 详情
(IX) 65759     C26H31ClN2O2 详情 详情
Extended Information