Sodium Carbonate → HCID 59496097, 화합물

HRID 1513348

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HRID 1513348 반응식
Br[C:2]1[C:3](=[O:28])[NH:4][C:5](=[O:27])[N:6]([CH2:8][CH2:9][CH2:10][N:11]2[CH2:16][C@H:15]3[C@:13]([C:17]4[CH:22]=[CH:21][C:20]([C:23]([F:26])([F:25])[F:24])=[CH:19][CH:18]=4)([CH2:14]3)[CH2:12]2)[N:7]=1.[CH3:29][C:30]1[S:31][C:32](B2OC(C)(C)C(C)(C)O2)=[C:33]([CH3:35])[N:34]=1.C(=O)([O-])[O-].[Na+].[Na+].C1(C2C=CC=CC=2)C=CC=CC=1P(C1CCCCC1)C1CCCCC1>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O.COCCOC>[CH3:29][C:30]1[S:31][C:32]([C:2]2[C:3](=[O:28])[NH:4][C:5](=[O:27])[N:6]([CH2:8][CH2:9][CH2:10][N:11]3[CH2:16][C@H:15]4[C@:13]([C:17]5[CH:18]=[CH:19][C:20]([C:23]([F:26])([F:24])[F:25])=[CH:21][CH:22]=5)([CH2:14]4)[CH2:12]3)[N:7]=2)=[C:33]([CH3:35])[N:34]=1

참가 물질

8

반응물 4

HCID 10340Sodium Carbonate2회HCID 27342162-(Dicyclohexylphosphino)biphenyl2회HCID 185257002,4-Dimethyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,3-thiazole2회HCID 59496096HCID 59496096, 화합물

생성물 1

HCID 59496097HCID 59496097, 화합물수율 24.35%

시약·촉매·용매 3

HCID 178418397HCID 178418397, 화합물촉매2회HCID 962Water용매HCID 80711,2-Dimethoxyethane용매

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온도
90 °C

실험 절차

6-bromo-2-(3-{(1S,5R)-1-[4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hex-3-yl}propyl)-1,2,4-triazine-3,5(2H,4H)-dione (P8, 170 mg, 0.370 mmol) was suspended in a degassed mixture of 1,2-Dimethoxyethane (DME) (6169 ply Water (1234 μl), then 2,4-dimethyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,3-thiazole (266 mg, 1.110 mmol), SODIUM CARBONATE (118 mg, 1.110 mmol), 2-biphenylyl(dicyclohexyl)phosphane (25.9 mg, 0.074 mmol) and Tetrakis (86 mg, 0.074 mmol) were added. The mixture was then heated at 90° C. and stirred at that temperature for 3 hours. Then the reaction mixture was cooled down to room temperature and 2,4-dimethyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,3-thiazole (266 mg, 1.110 mmol), 2-biphenylyl(dicyclohexyl)phosphane (25.9 mg, 0.074 mmol), SODIUM CARBONATE (118 mg, 1.110 mmol) and Tetrakis (86 mg, 0.074 mmol) were added again. The mixture was stirred at 90° C. for further 4 hours, then left stirring at room temperature overnight. The mixture was concentrated under reduced pressure and partitioned between AcOEt and water. Phases were separated, organic phase was dried over sodium sulphate and concentrated under reduced pressure. Crude product was purified by Preparative HPLC then further purified by flash chromatography (SiO2; eluent: DCM to DCM/MeOH 9:1) affording 6-(2,4-dimethyl-1,3-thiazol-5-yl)-2-(3-{(1S,5R)-1-[4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hex-3-yl}propyl)-1,2,4-triazine-3,5(2H,4H)-dione (E7, 44.3 mg, 0.090 mmol, 24.35% yield).

후처리

  1. temperatureThen the reaction mixture was cooled down to room temperature
  2. stirringThe mixture was stirred at 90° C. for further 4 hours
  3. waitleft
  4. stirringstirring at room temperature overnight
  5. concentrationThe mixture was concentrated under reduced pressure
  6. custompartitioned between AcOEt and water
  7. customPhases were separated
  8. dry with materialorganic phase was dried over sodium sulphate
  9. concentrationconcentrated under reduced pressure
  10. customCrude product was purified by Preparative HPLC
  11. customthen further purified by flash chromatography (SiO2; eluent: DCM to DCM/MeOH 9:1)

출처 및 근거

ORD 기록
ord-0bff464b7f834586abed202d185f3fe2
출처 데이터셋
uspto-grants-2012_07
특허 번호
US08217168B2

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