Methanesulfonyl chloride → Methanesulfonic acid 3-{1-[(R)-3-(2-{4-[1-(2-ethoxy-ethyl)-1H-benzoimidazol-2-yl]-[1,4]diazepan-1-yl}-ethyl)-3-phenyl-pyrrolidin-1-yl]-methanoyl}-4-methoxy-phenyl Ester

HRID 2230724노트

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HRID 2230724 반응식
[CH2:1]([O:3][CH2:4][CH2:5][N:6]1[C:10]2[CH:11]=[CH:12][CH:13]=[CH:14][C:9]=2[N:8]=[C:7]1[N:15]1[CH2:21][CH2:20][CH2:19][N:18]([CH2:22][CH2:23][C@:24]2([C:40]3[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=3)[CH2:28][CH2:27][N:26]([C:29]([C:31]3[CH:36]=[C:35]([OH:37])[CH:34]=[CH:33][C:32]=3[O:38][CH3:39])=[O:30])[CH2:25]2)[CH2:17][CH2:16]1)[CH3:2].C(N(C(C)C)CC)(C)C.[CH3:55][S:56](Cl)(=[O:58])=[O:57]>ClCCl>[CH2:1]([O:3][CH2:4][CH2:5][N:6]1[C:10]2[CH:11]=[CH:12][CH:13]=[CH:14][C:9]=2[N:8]=[C:7]1[N:15]1[CH2:21][CH2:20][CH2:19][N:18]([CH2:22][CH2:23][C@:24]2([C:40]3[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=3)[CH2:28][CH2:27][N:26]([C:29]([C:31]3[CH:36]=[C:35]([O:37][S:56]([CH3:55])(=[O:58])=[O:57])[CH:34]=[CH:33][C:32]=3[O:38][CH3:39])=[O:30])[CH2:25]2)[CH2:17][CH2:16]1)[CH3:2]

참가 물질

5

반응물 3

HCID 31297Methanesulfonyl chlorideHCID 81531DiisopropylethylamineHCID 701487941-[(R)-3-(2-{4-[1-(2-ethoxy-ethyl)-1H-benzoimidazol-2-yl]-[1,4]diazepan-1-yl}-ethyl)-3-phenyl-pyrrolidin-1-yl]-1-(5-hydroxy-2-methoxy-phenyl)-methanone

생성물 1

HCID 59902263Methanesulfonic acid 3-{1-[(R)-3-(2-{4-[1-(2-ethoxy-ethyl)-1H-benzoimidazol-2-yl]-[1,4]diazepan-1-yl}-ethyl)-3-phenyl-pyrrolidin-1-yl]-methanoyl}-4-methoxy-phenyl Ester수율 125.2%

시약·촉매·용매 1

HCID 6344Dichloromethane용매2회

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온도
0 °C

실험 절차

Treat a stirred solution of 1-[(R)-3-(2-{4-[1-(2-ethoxy-ethyl)-1H-benzoimidazol-2-yl]-[1,4]diazepan-1-yl}-ethyl)-3-phenyl-pyrrolidin-1-yl]-1-(5-hydroxy-2-methoxy-phenyl)-methanone (0.25 g, 0.22 mmol) and dichloromethane (5 mL) at 0° C. with diisopropylethylamine (0.14 mL, 0.84 mmol) and methane sulfonyl chloride (0.04 mL, 0.5 mmol). Stir the reaction mixture at 0° C. for two hours, dilute with dichloromethane and wash with water. Dry (MgSO4) the organic phase, filter and concentrate the filtrate in vacuo. Purify the product by column chromatography (silica gel, elute sequentially with 3% methanol in dichloromethane then with 5% methanol in dichloromethane) and concentrate the appropriate fractions to afford 0.19 g of the title compound, Rf=0.28 (silica gel, 5% methanol in dichloromethane). The compound may be converted to the dihydrochloride salt by methods swell known in the art.

후처리

  1. washwash with water
  2. dry with materialDry (MgSO4) the organic phase
  3. filtrationfilter
  4. concentrationconcentrate the filtrate in vacuo
  5. customPurify the product by column chromatography (silica gel
  6. washelute sequentially with 3% methanol in dichloromethane
  7. concentrationwith 5% methanol in dichloromethane) and concentrate the appropriate fractions

출처 및 근거

ORD 기록
ord-d8a75b4628324e1c8aa2cac7d03ca4dc
출처 데이터셋
uspto-grants-2002_07
특허 번호
US06423704B1

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