Water → (R)-N-(4-(Dimethylcarbamoyl)phenyl)-1-(4-(trifluoromethyl)phenyl)-3,4-dihydroisoquinoline-2(1H)-carboxamide

HRID 445342노트

반응식

HRID 445342 반응식
[NH2:1][C:2]1[CH:12]=[CH:11][C:5]([C:6]([N:8]([CH3:10])[CH3:9])=[O:7])=[CH:4][CH:3]=1.[H-].[Na+].[F:15][C:16]([F:46])([F:45])[C:17]1[CH:22]=[CH:21][C:20]([C@@H:23]2[C:32]3[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=3)[CH2:26][CH2:25][N:24]2[C:33](OC2C=CC([N+]([O-])=O)=CC=2)=[O:34])=[CH:19][CH:18]=1.O>C1COCC1>[CH3:9][N:8]([CH3:10])[C:6]([C:5]1[CH:11]=[CH:12][C:2]([NH:1][C:33]([N:24]2[CH2:25][CH2:26][C:27]3[C:32](=[CH:31][CH:30]=[CH:29][CH:28]=3)[C@H:23]2[C:20]2[CH:21]=[CH:22][C:17]([C:16]([F:45])([F:15])[F:46])=[CH:18][CH:19]=2)=[O:34])=[CH:3][CH:4]=1)=[O:7]

참가 물질

6

반응물 4

HCID 962WaterHCID 24758Sodium hydrideHCID 2355274-Amino-N,N-dimethylbenzamideHCID 59536297(R)-4-Nitrophenyl 1-(4-(trifluoromethyl)phenyl)-3,4-dihydroisoquinoline-2(1H)-carboxylate

생성물 1

HCID 59536420(R)-N-(4-(Dimethylcarbamoyl)phenyl)-1-(4-(trifluoromethyl)phenyl)-3,4-dihydroisoquinoline-2(1H)-carboxamide

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

실험 절차

To a solution of 4-amino-N,N-dimethylbenzamide (74 mg, 452 μmol) in THF (0.5 mL) was added sodium hydride, 60% dispersion in mineral oil (19 μL, 452 μmol). The resulting mixture was then subjected to a microwave irradiation at 150° C. for 5 min. Then, (R)-4-nitrophenyl 1-(4-(trifluoromethyl)phenyl)-3,4-dihydroisoquinoline-2(1H)-carboxylate (100 mg, 226 μmol, example 88) was added and the mixture was stirred at RT for overnight. Then, H2O (0.5 mL) was added slowly and the mixture was extracted with EtOAc (2×1 mL). The combined organic extracts were dried over MgSO4 and concentrated. The residue was dissolved in DMSO (1.0 mL) and the solution mixture was then purified by preparative HPLC (0%-100% MeCN 0.1% TFA/H2O 0.1% TFA) to give the desired compound, which was dissolved in MeOH (1.0 mL). Then, the solution was washed through PL-HCO3 MP-Resin (200 mg per 6 mL tube) and the resin was washed with MeOH (2×0.3 mL). The combined washings were concentrated and dried under vacuum to give the title compound as light brown solid. MS (ESI, positive ion) m/z: 468 (M+H).

후처리

  1. customThe resulting mixture was then subjected to a microwave irradiation at 150° C. for 5 min
  2. extractionthe mixture was extracted with EtOAc (2×1 mL)
  3. dry with materialThe combined organic extracts were dried over MgSO4
  4. concentrationconcentrated
  5. dissolutionThe residue was dissolved in DMSO (1.0 mL)
  6. customthe solution mixture was then purified by preparative HPLC (0%-100% MeCN 0.1% TFA/H2O 0.1% TFA)

출처 및 근거

ORD 기록
ord-db210f1ab71c413b895c6746c8b271b5
출처 데이터셋
uspto-grants-2013_07
특허 번호
US08476297B2

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