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【结 构 式】

【分子编号】29450

【品名】benzyl 2-[[(4-benzylbenzyl)(methoxy)phosphoryl]methyl]-4-phenylbutanoate

【CA登记号】

【 分 子 式 】C33H35O4P

【 分 子 量 】526.612262

【元素组成】C 75.27% H 6.7% O 12.15% P 5.88%

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:(VII)

Michael addition of bis(trimethylsilyl)phosphonite (II) to benzyl 2-phenethylacrylate (I) afforded phosphinic acid (III). 4-Benzoylbenzyl bromide (IV) was reduced using triethylsilane and trifluoroacetic acid to give 4-benzylbenzyl bromide (V). Subsequent Arbuzov reaction of phosphinic acid (III) with bromide (V) generated the disubstituted phosphinic acid (VI), which was protected as the methyl ester (VII) employing trimethylsilyl diazomethane. Hydrogenolysis of the benzyl ester of (VII) then yielded carboxylic acid (VIII). This was coupled with (S)-tert-leucinamide (IX) by means of BOP to furnish the corresponding diamide (X). Alternatively, acid (VIII) was treated with N-hydroxysuccinimide (NHS) and EDC, and the resulting succinimidyl ester (XI) was coupled with amine (IX) to produce (X). The methyl phosphinate ester (X) was then deprotected by treatment with aqueous trifluoroacetic acid, and the required (S,S)-diastereoisomer was isolated by reverse phase flash chromatography.

1 Reiter, L.A.; Rizzi, J.P.; Pandit, J.; et al.; Inhibition of MMP-1 and MMP-13 with phosphinic acids that exploit binding in the S2 pocket. Bioorg Med Chem Lett 1999, 9, 2, 127.
2 Reiter, L.A. (Pfizer Inc.); Phosphinate based inhibitors of matrix metalloproteases. EP 0923585; JP 1999514673; WO 9803516 .
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(A) 29448 trimethyl-N-[(Z)-1-(trimethylsilyl)ethylidene]silanamineN-(trimethylsilyl)-N-[(Z)-1-(trimethylsilyl)ethylidene]amine C8H21NSi2 详情 详情
(I) 29443 benzyl 2-phenethylacrylate C18H18O2 详情 详情
(II) 29444 bis[(trimethylsilyl)methyl]phosphine C8H23PSi2 详情 详情
(III) 29445 2-[(benzyloxy)carbonyl]-4-phenylbutylphosphinic acid C18H21O4P 详情 详情
(IV) 29446 [4-(bromomethyl)phenyl](phenyl)methanone C14H11BrO 详情 详情
(V) 29447 1-benzyl-4-(bromomethyl)benzene C14H13Br 详情 详情
(VI) 29449 4-benzylbenzyl[2-[(benzyloxy)carbonyl]-4-phenylbutyl]phosphinic acid C32H33O4P 详情 详情
(VII) 29450 benzyl 2-[[(4-benzylbenzyl)(methoxy)phosphoryl]methyl]-4-phenylbutanoate C33H35O4P 详情 详情
(VIII) 29451 2-[[(4-benzylbenzyl)(methoxy)phosphoryl]methyl]-4-phenylbutyric acid C26H29O4P 详情 详情
(IX) 18843 (2S)-2-amino-N,3,3-trimethylbutanamide 89226-12-0 C7H16N2O 详情 详情
(X) 29452 methyl 4-benzylbenzyl[2-[([(1S)-2,2-dimethyl-1-[(methylamino)carbonyl]propyl]amino)carbonyl]-4-phenylbutyl]phosphinate C33H43N2O4P 详情 详情
(XI) 29453 methyl 4-benzylbenzyl(2-[[(2,5-dioxo-1-pyrrolidinyl)oxy]carbonyl]-4-phenylbutyl)phosphinate C30H32NO6P 详情 详情
Extended Information