4-Methylmorpholine → [4-(3-Methanesulfonyl-phenoxy)-phenyl]-(2-(S)-pyrrolidin-1-ylmethyl-pyrrolidin-1-yl)-methanone hydrochloride

HRID 552589

反応式

HRID 552589 の反応式
[CH3:1][S:2]([C:5]1[CH:6]=[C:7]([CH:18]=[CH:19][CH:20]=1)[O:8][C:9]1[CH:17]=[CH:16][C:12]([C:13]([OH:15])=O)=[CH:11][CH:10]=1)(=[O:4])=[O:3].C(Cl)(=O)C([Cl:24])=O.[NH:27]1[CH2:31][CH2:30][CH2:29][C@H:28]1[CH2:32][N:33]1[CH2:37][CH2:36][CH2:35][CH2:34]1.CN1CCOCC1>ClCCl.CN(C)C=O>[ClH:24].[CH3:1][S:2]([C:5]1[CH:6]=[C:7]([CH:18]=[CH:19][CH:20]=1)[O:8][C:9]1[CH:10]=[CH:11][C:12]([C:13]([N:27]2[CH2:31][CH2:30][CH2:29][C@H:28]2[CH2:32][N:33]2[CH2:37][CH2:36][CH2:35][CH2:34]2)=[O:15])=[CH:16][CH:17]=1)(=[O:3])=[O:4]

参加物

7

反応物 4

HCID 79724-MethylmorpholineHCID 65578Oxalyl chlorideHCID 853152(S)-(+)-1-(2-Pyrrolidinylmethyl)pyrrolidineHCID 43807118HCID 43807118、化合物2 回

生成物 1

HCID 11960748[4-(3-Methanesulfonyl-phenoxy)-phenyl]-(2-(S)-pyrrolidin-1-ylmethyl-pyrrolidin-1-yl)-methanone hydrochloride

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide触媒HCID 6344Dichloromethane溶媒2 回

実験手順

4-(3-Methanesulfonyl-phenoxy)-benzoic acid (1.0 mmol) (see Intermediate 13) and oxalyl chloride (2.0 mmol) are combined in dichloromethane (0.10 M), add 1 drop of dimethylformamide added as a catalyst. The solution is stirred at room temperature for 2 h. The reaction is concentrated in vacuo. The resulting residue is dissolved in dichloromethane and added to a stirring solution of (S)-(+)-1-(2-pyrrolidinylmethyl)pyrrolidine (1.0 mmol) and N-methylmorpholine (1.0 mmol) in dichloromethane (0.10 M). The reaction is stirred at room temperature for 18 h. The reaction is washed with saturated aqueous sodium bicarbonate and the aqueous portion extracted with 10% isopropanol/dichloromethane. The combined organic portions are concentrated in vacuo and purified via radial chromatography eluting with 2 M ammonia in methanol and dichloromethane. The purified free base is dissolved in a minimal amount of dichloromethane and a slight excess of 1 M HCl in ether is added, followed by hexane. The mixture is then concentrated in vacuo to give the titled compound. MS (m/e): 429.2 (M+1)

後処理

  1. additionadded as a catalyst
  2. concentrationThe reaction is concentrated in vacuo
  3. dissolutionThe resulting residue is dissolved in dichloromethane
  4. stirringThe reaction is stirred at room temperature for 18 h
  5. washThe reaction is washed with saturated aqueous sodium bicarbonate
  6. extractionthe aqueous portion extracted with 10% isopropanol/dichloromethane
  7. concentrationThe combined organic portions are concentrated in vacuo
  8. custompurified via radial chromatography
  9. washeluting with 2 M ammonia in methanol and dichloromethane
  10. dissolutionThe purified free base is dissolved in a minimal amount of dichloromethane
  11. additiona slight excess of 1 M HCl in ether is added
  12. concentrationThe mixture is then concentrated in vacuo

出典と根拠

ORDレコード
ord-bf8c203509b94f3da81e08680840b2de
出典データセット
uspto-grants-2011_05
特許番号
US07951826B2

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