Methyl malonyl chloride → 3-[2-(4-Benzyloxyphenyl)-1-cyclohexyl-1H-benzimidazole-5-sulfonylamino]-3-oxo-propionic acid methyl ester

HRID 392992

반응식

HRID 392992 반응식
[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]2[N:19]([CH:20]3[CH2:25][CH2:24][CH2:23][CH2:22][CH2:21]3)[C:18]3[CH:26]=[CH:27][C:28]([S:30]([NH2:33])(=[O:32])=[O:31])=[CH:29][C:17]=3[N:16]=2)=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[CH3:44][O:45][C:46](=[O:51])[CH2:47][C:48](Cl)=[O:49]>ClCCl>[CH3:44][O:45][C:46](=[O:51])[CH2:47][C:48]([NH:33][S:30]([C:28]1[CH:27]=[CH:26][C:18]2[N:19]([CH:20]3[CH2:21][CH2:22][CH2:23][CH2:24][CH2:25]3)[C:15]([C:12]3[CH:11]=[CH:10][C:9]([O:8][CH2:1][C:2]4[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=4)=[CH:14][CH:13]=3)=[N:16][C:17]=2[CH:29]=1)(=[O:32])=[O:31])=[O:49]

참가 물질

5

반응물 3

HCID 123460Methyl malonyl chlorideHCID 2733832Lithium HexamethyldisilazideHCID 226608052-[4-(Benzyloxy)phenyl]-1-cyclohexyl-1H-benzimidazole-5-sulfonamide

생성물 1

HCID 698964073-[2-(4-Benzyloxyphenyl)-1-cyclohexyl-1H-benzimidazole-5-sulfonylamino]-3-oxo-propionic acid methyl ester수율 7%

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

A solution of intermediate 69 (0.046 g, 0.1 mmol) in dichloromethane (0.700 mL) was cooled to 0° C. Lithium bis(trimethylsilyl)amide (1.0 M solution in tetrahydrofuran) (0.10 ml, 0.10 mmol) was added and the mixture was stirred for 1 hr. Methyl-3-chloro-3-oxo-propionate (0.011 ml, 0.10 mmol was added. The reaction mixture was stirred at rt overnight. The reaction mixture was concentrated and the residue purified by reverse phase HPLC (C18 column, water/acetonitrile gradient containing 0.05% trifluoroacetic acid) to afford the product (0.005 g, 7%). 1H NMR (CDCl3) δ 8.60 (s, 1H), 8.16 (d, 1H, J=8.8 Hz), 7.85 (d, 1H, J=8.8 Hz), 7.64 (d, 2H, J=8.8 Hz), 7.50-7.38 (m, 5H), 7.21 (d, 2H, J=8.8 Hz), 5.18 (s, 2H), 4.49 (m, 1H), 3.70 (s, 3H), 3.35 (s, 2H), 2.30 (br m, 2H), 2.02 (br m, 4H), 1.82 (br m, 1H), 1.35 (br m, 3H); ESI-MS m/e 562.18(M+1); HPLC purity (UV) 99%.

후처리

  1. stirringThe reaction mixture was stirred at rt overnight
  2. concentrationThe reaction mixture was concentrated
  3. customthe residue purified by reverse phase HPLC (C18 column, water/acetonitrile gradient containing 0.05% trifluoroacetic acid)

출처 및 근거

ORD 기록
ord-3152a617be2543aa8943526729575420
출처 데이터셋
uspto-grants-2004_10
특허 번호
US06803374B2

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