Sodium hydride → 1,1-Dimethylethyl 3-(5-{5-[3-cyano-4-(3-fluoro-1-pyrrolidinyl)phenyl]-1,2,4-oxadiazol-3-yl}-1-isoquinolinyl)propanoate

HRID 2192507노트

반응식

HRID 2192507 반응식
[F:1][CH:2]1[CH2:6][CH2:5][NH:4][CH2:3]1.[H-].[Na+].[C:9]([C:11]1[CH:12]=[C:13]([C:18]2[O:22][N:21]=[C:20]([C:23]3[CH:32]=[CH:31][CH:30]=[C:29]4[C:24]=3[CH:25]=[CH:26][N:27]=[C:28]4[CH2:33][CH2:34][C:35]([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:36])[N:19]=2)[CH:14]=[CH:15][C:16]=1F)#[N:10]>CN(C=O)C>[C:9]([C:11]1[CH:12]=[C:13]([C:18]2[O:22][N:21]=[C:20]([C:23]3[CH:32]=[CH:31][CH:30]=[C:29]4[C:24]=3[CH:25]=[CH:26][N:27]=[C:28]4[CH2:33][CH2:34][C:35]([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:36])[N:19]=2)[CH:14]=[CH:15][C:16]=1[N:4]1[CH2:5][CH2:6][CH:2]([F:1])[CH2:3]1)#[N:10]

참가 물질

5

반응물 3

HCID 24758Sodium hydride2회HCID 3744989Pyrrolidine, 3-fluoro-HCID 581499101,1-Dimethylethyl 3-{5-[5-(3-cyano-4-fluorophenyl)-1,2,4-oxadiazol-3-yl]-1-isoquinolinyl}propanoate

생성물 1

HCID 581499051,1-Dimethylethyl 3-(5-{5-[3-cyano-4-(3-fluoro-1-pyrrolidinyl)phenyl]-1,2,4-oxadiazol-3-yl}-1-isoquinolinyl)propanoate수율 21%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

A solution of 3-fluoropyrrolidine (Anichem Product List; 16.39 mg, 0.130 mmol) in DMF (2.5 ml) was cooled in an ice bath and sodium hydride (6.89 mg, 0.172 mmol) was added. The mixture was stirred for 10 mins then 1,1-dimethylethyl 3-{5-[5-(3-cyano-4-fluorophenyl)-1,2,4-oxadiazol-3-yl]-1-isoquinolinyl}propanoate (D50; 58 mg, 0.130 mmol) was added. The ice bath was removed and the solution was stirred at room temperature for 3 hrs. Further sodium hydride (3.13 mg, 0.078 mmol) was added and the resulting solution was stirred at room temperature overnight. The mixture was partitioned between ethyl acetate and brine. The organic layer was dried with magnesium sulphate and concentrated under vacuum. The residue was purified by Mass-Directed Auto-Preparative HPLC (formic acid modifier) to provide the title compound as a cream solid (14 mg).

후처리

  1. customThe ice bath was removed
  2. stirringthe solution was stirred at room temperature for 3 hrs
  3. stirringthe resulting solution was stirred at room temperature overnight
  4. customThe mixture was partitioned between ethyl acetate and brine
  5. dry with materialThe organic layer was dried with magnesium sulphate
  6. concentrationconcentrated under vacuum
  7. customThe residue was purified by Mass-Directed Auto-Preparative HPLC (formic acid modifier)

출처 및 근거

ORD 기록
ord-9df46e3e6782486baa6da6e702e2e47f
출처 데이터셋
uspto-grants-2012_12
특허 번호
US08329730B2

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