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

HRID 445342ノート

反応式

HRID 445342 の反応式
[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]

参加物

6

反応物 4

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

生成物 1

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

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

実験手順

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).

後処理

  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)

出典と根拠

ORDレコード
ord-db210f1ab71c413b895c6746c8b271b5
出典データセット
uspto-grants-2013_07
特許番号
US08476297B2

反応ノート

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