Sodium Carbonate → 6-(2-fluoro-3-pyridinyl)-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

HRID 1513350ノート

反応式

HRID 1513350 の反応式
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.[F:29][C:30]1[C:35](B(O)O)=[CH:34][CH:33]=[CH:32][N:31]=1.C(=O)([O-])[O-].[Na+].[Na+].C1(C2C=CC=CC=2)C=CC=CC=1P(C1CCCCC1)C1CCCCC1>COCCOC.O.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>[F:29][C:30]1[C:35]([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:22]=[CH:21][C:20]([C:23]([F:26])([F:25])[F:24])=[CH:19][CH:18]=5)([CH2:14]4)[CH2:12]3)[N:7]=2)=[CH:34][CH:33]=[CH:32][N:31]=1

参加物

9

反応物 4

HCID 10340Sodium Carbonate2 回HCID 27342162-(Dicyclohexylphosphino)biphenyl2 回HCID 27832702-Fluoropyridine-3-boronic acid2 回HCID 594960966-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

生成物 1

HCID 594960896-(2-fluoro-3-pyridinyl)-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収率 45.4%

試薬・触媒・溶媒 4

HCID 178418397HCID 178418397、化合物触媒2 回HCID 962Water溶媒HCID 80711,2-Dimethoxyethane溶媒HCID 18180031Water 1,2-dimethoxyethane溶媒

反応条件

温度
90 °C

実験手順

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, 100 mg, 0.218 mmol) was suspended in a degassed mixture of 1,2-Dimethoxyethane (DME) (3.629 ml)/Water (0.726 ml). Then (2-fluoro-3-pyridinyl)boronic acid (92 mg, 0.653 mmol), sodium carbonate (69.2 mg, 0.653 mmol), Tetrakis (50.3 mg, 0.044 mmol) and 2-biphenylyl(dicyclohexyl)phosphane (15.26 mg, 0.044 mmol) were added and the mixture was heated to 90° C. and stirred at that temperature for 3 hours. The mixture was cooled down to room temperature, diluted with 1.3 mL of a mixture of DME/Water (5:1) then 2-biphenylyl(dicyclohexyl)phosphane (15.26 mg, 0.044 mmol), (2-fluoro-3-pyridinyl)boronic acid (92 mg, 0.653 mmol), Tetrakis (50.3 mg, 0.044 mmol) and sodium carbonate (69.2 mg, 0.653 mmol) were added again. The reaction mixture was heated to 90° C. and left stirring at that temperature for 40 minutes. The reaction mixture was cooled down to room temperature and evaporated under reduced pressure. The residue was partitioned between AcOEt and water and extracted. Organic phase was dried over sodium sulphate, filtered and concentrated under reduced pressure. Crude product was purified by Preparative HPLC affording 6-(2-fluoro-3-pyridinyl)-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 (E9, 47 mg, 0.099 mmol, 45.4% yield).

後処理

  1. temperatureThe mixture was cooled down to room temperature
  2. temperatureThe reaction mixture was heated to 90° C.
  3. waitleft
  4. stirringstirring at that temperature for 40 minutes
  5. temperatureThe reaction mixture was cooled down to room temperature
  6. customevaporated under reduced pressure
  7. customThe residue was partitioned between AcOEt and water
  8. extractionextracted
  9. dry with materialOrganic phase was dried over sodium sulphate
  10. filtrationfiltered
  11. concentrationconcentrated under reduced pressure
  12. customCrude product was purified by Preparative HPLC

出典と根拠

ORDレコード
ord-187729a08a2f45919c54b3024d1a7cad
出典データセット
uspto-grants-2012_07
特許番号
US08217168B2

反応ノート

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