Triethylamine → 7-{3-[1-(3-cyanophenylcarbamoyl)-pyrrolidin-2-yl]-benzoylamino}-3,4-dihydro-1H-isoquinoline-2-carboxylic acid benzyl ester

HRID 1524297노트

반응식

HRID 1524297 반응식
Cl.[CH2:2]([O:9][C:10]([N:12]1[CH2:21][CH2:20][C:19]2[C:14](=[CH:15][C:16]([NH:22][C:23](=[O:35])[C:24]3[CH:29]=[CH:28][CH:27]=[C:26]([CH:30]4[CH2:34][CH2:33][CH2:32][NH:31]4)[CH:25]=3)=[CH:17][CH:18]=2)[CH2:13]1)=[O:11])[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.CCN(CC)CC.[C:43]([C:45]1[CH:46]=[C:47]([N:51]=[C:52]=[O:53])[CH:48]=[CH:49][CH:50]=1)#[N:44].[N-]=C=O>CN(C=O)C>[CH2:2]([O:9][C:10]([N:12]1[CH2:21][CH2:20][C:19]2[C:14](=[CH:15][C:16]([NH:22][C:23](=[O:35])[C:24]3[CH:29]=[CH:28][CH:27]=[C:26]([CH:30]4[CH2:34][CH2:33][CH2:32][N:31]4[C:52](=[O:53])[NH:51][C:47]4[CH:48]=[CH:49][CH:50]=[C:45]([C:43]#[N:44])[CH:46]=4)[CH:25]=3)=[CH:17][CH:18]=2)[CH2:13]1)=[O:11])[C:3]1[CH:4]=[CH:5][CH:6]=[CH:7][CH:8]=1

참가 물질

6

반응물 4

HCID 8471TriethylamineHCID 105034IsocyanateHCID 27333153-IsocyanatobenzonitrileHCID 666549657-(3-pyrrolidin-2-yl-benzoylamino)-3,4-dihydro-1H-isoquinoline-2-carboxylic acid benzyl ester HCl

생성물 1

HCID 666557477-{3-[1-(3-cyanophenylcarbamoyl)-pyrrolidin-2-yl]-benzoylamino}-3,4-dihydro-1H-isoquinoline-2-carboxylic acid benzyl ester수율 80.1%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

To a solution of 7-(3-pyrrolidin-2-yl-benzoylamino)-3,4-dihydro-1H-isoquinoline-2-carboxylic acid benzyl ester HCl (238 mg, 0.387 mmol) in DMF (5 mL) add Et3N (0.082 mL, 0.581 mmol) followed by 3-cyanophenyl isocyanate (69 mg, 0.464 mmol). Stir the solution at room temperature for 48 h. LCMS analysis indicates the presence of starting material. Add more isocyanate (69 mg, 0.464 mmol) and stir the reaction at room temperature 24 h more. Quench the reaction with sat. NH4Cl (100 mL) and extract with EtOAc (2×150 mL). Wash the organic layers with water (100 mL), dry (Na2SO4) and concentrate to an oil. Purify the crude product by silica gel chromatography eluting with 10% to 75% EtOAc/hexane to afford 186 mg 7-{3-[1-(3-cyanophenylcarbamoyl)-pyrrolidin-2-yl]-benzoylamino}-3,4-dihydro-1H-isoquinoline-2-carboxylic acid benzyl ester as a solid foam.

후처리

  1. stirringstir
  2. customthe reaction at room temperature 24 h more
  3. customQuench
  4. customthe reaction with sat. NH4Cl (100 mL)
  5. extractionextract with EtOAc (2×150 mL)
  6. washWash the organic layers with water (100 mL)
  7. dry with materialdry (Na2SO4)
  8. concentrationconcentrate to an oil
  9. customPurify the crude product by silica gel chromatography
  10. washeluting with 10% to 75% EtOAc/hexane

출처 및 근거

ORD 기록
ord-9215c195659e401d9bdad11b97d38591
출처 데이터셋
uspto-grants-2015_07
특허 번호
US09079880B2

반응 노트

불러오는 중…