1,2-Dichloroethane → 7-[3-(1-tert-butoxycarbonyl-pyrrolidin-2-yl)-benzoylamino]-3,4-dihydro-1H-isoquinoline-2-carboxylic acid benzyl ester

HRID 1524294노트

반응식

HRID 1524294 반응식
[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][CH2:10][CH:9]1[C:13]1[CH:18]=[CH:17][CH:16]=[C:15]([C:19](O)=[O:20])[CH:14]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.CCN(CC)CC.[CH2:43]([O:50][C:51]([N:53]1[CH2:62][CH2:61][C:60]2[C:55](=[CH:56][C:57]([NH2:63])=[CH:58][CH:59]=2)[CH2:54]1)=[O:52])[C:44]1[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=1>CN(C=O)C.CCOC(C)=O>[CH2:43]([O:50][C:51]([N:53]1[CH2:62][CH2:61][C:60]2[C:55](=[CH:56][C:57]([NH:63][C:19](=[O:20])[C:15]3[CH:16]=[CH:17][CH:18]=[C:13]([CH:9]4[CH2:10][CH2:11][CH2:12][N:8]4[C:6]([O:5][C:1]([CH3:3])([CH3:2])[CH3:4])=[O:7])[CH:14]=3)=[CH:58][CH:59]=2)[CH2:54]1)=[O:52])[C:44]1[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=1

참가 물질

8

반응물 5

HCID 111,2-DichloroethaneHCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 450739843-{1-[(Tert-butoxy)carbonyl]pyrrolidin-2-yl}benzoic acidHCID 53419255Benzyl 7-amino-3,4-dihydroisoquinoline-2(1H)-carboxylate

생성물 1

HCID 666551417-[3-(1-tert-butoxycarbonyl-pyrrolidin-2-yl)-benzoylamino]-3,4-dihydro-1H-isoquinoline-2-carboxylic acid benzyl ester수율 96.5%

시약·촉매·용매 2

HCID 6228Dimethylformamide용매2회HCID 8857Ethyl Acetate용매

실험 절차

To a solution of 2-(3-carboxy-phenyl)-pyrrolidine-1-carboxylic acid tert-butyl ester (500 mg, 1.682 mmol), EDC (346 mg, 1.766 mmol), and HOBt (240 mg, 1.682 mmol) in DMF (5 mL) add Et3N (0.355 mL, 2.523 mmol) and stir the solution at room temperature for 15 min. To this add a solution of the 7-amino-3,4-dihydro-1H-isoquinoline-2-carboxylic acid benzyl ester (500 mg, 1.682 mmol) as a solution in DMF (5 mL) and stir the solution at 65° C. for 24 h. Dilute the reaction with EtOAc (250 mL) and wash with sat. NH4Cl (250 mL), sat. NaHCO3 (250 mL), then water (250 mL). Extract the aqueous layers with more EtOAc (250 mL) and dry the combined organics (Na2SO4), and concentrate in vacuo to give 902 mg of 7-[3-(1-tert-butoxycarbonyl-pyrrolidin-2-yl)-benzoylamino]-3,4-dihydro-1H-isoquinoline-2-carboxylic acid benzyl ester as a solid.

후처리

  1. stirringstir the solution at 65° C. for 24 h
  2. additionDilute
  3. washwash with sat. NH4Cl (250 mL), sat. NaHCO3 (250 mL)
  4. extractionExtract the aqueous layers with more EtOAc (250 mL)
  5. dry with materialdry the combined organics (Na2SO4)
  6. concentrationconcentrate in vacuo

출처 및 근거

ORD 기록
ord-2bf05f732927415cbfc8c38130750f9d
출처 데이터셋
uspto-grants-2015_07
특허 번호
US09079880B2

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