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 2230724ノート

反応式

HRID 2230724 の反応式
[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]

参加物

5

反応物 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

生成物 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 Ester収率 125.2%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒2 回

反応条件

温度
0 °C

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-d8a75b4628324e1c8aa2cac7d03ca4dc
出典データセット
uspto-grants-2002_07
特許番号
US06423704B1

反応ノート

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