Tetrahydrofuran → (7R,8aS)-7-[(5-cyclopropylpyrazin-2-yl)oxy]-2-[3-(trifluoromethyl)benzyl]-hexahydropyrrolo[1,2-a]pyrazin-3(4H)-one

HRID 1184619ノート

反応式

HRID 1184619 の反応式
[CH:1]1([C:4]2[N:5]=[CH:6][C:7]([O:10][C@H:11]3[CH2:20][N:14]4[CH2:15][C:16](=[O:19])[NH:17][CH2:18][C@@H:13]4[CH2:12]3)=[N:8][CH:9]=2)[CH2:3][CH2:2]1.O1CCCC1.[H-].[Na+].Br[CH2:29][C:30]1[CH:35]=[CH:34][CH:33]=[C:32]([C:36]([F:39])([F:38])[F:37])[CH:31]=1>CN(C)C=O>[CH:1]1([C:4]2[N:5]=[CH:6][C:7]([O:10][C@H:11]3[CH2:20][N:14]4[CH2:15][C:16](=[O:19])[N:17]([CH2:29][C:30]5[CH:35]=[CH:34][CH:33]=[C:32]([C:36]([F:37])([F:38])[F:39])[CH:31]=5)[CH2:18][C@@H:13]4[CH2:12]3)=[N:8][CH:9]=2)[CH2:3][CH2:2]1

参加物

6

反応物 4

HCID 8028TetrahydrofuranHCID 24758Sodium hydrideHCID 1230611-(Bromomethyl)-3-(trifluoromethyl)benzeneHCID 86680536(7R,8aS)-7-[(5-cyclopropylpyrazin-2-yl)oxy]hexahydropyrrolo[1,2-a]-pyrazin-3(4H)-one

生成物 1

HCID 86680537(7R,8aS)-7-[(5-cyclopropylpyrazin-2-yl)oxy]-2-[3-(trifluoromethyl)benzyl]-hexahydropyrrolo[1,2-a]pyrazin-3(4H)-one

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

To a solution of the product from Example 201C (64 mg, 0.233 mmol) in 4:1 tetrahydrofuran:N,N-dimethylformamide (2 mL) was added sodium hydride (11.2 mg, 0.280 mmol). The resulting mixture was stirred at ambient temperate for 30 minutes, and 1-(bromomethyl)-3-(trifluoromethyl)benzene (42.8 μL, 0.280 mmol) was added. The mixture was stirred at ambient temperature for 1 hour and was then partitioned between water and ethyl acetate. The organic layer was dried over sodium sulfate, filtered, and concentrated in vacuo. The crude product was purified by chromatography on a 12 g silica gel column eluting with 5% ethyl acetate/hexanes for 3 minutes then a gradient to 100% ethyl acetate over 20 minutes. The title compound was obtained as a thick oil (13 mg, 13%). 1H NMR (300 MHz, methanol-d4) δ ppm 7.99 (dt, J=11.3, 5.7 Hz, 2H), 7.65-7.49 (m, 4H), 5.42 (dd, J=12.6, 5.1 Hz, 1H), 4.70 (d, J=3.7 Hz, 2H), 3.81-3.61 (m, 2H), 3.50-3.35 (m, 1H), 3.16 (dd, J=13.4, 8.3 Hz, 2H), 2.87 (qd, J=10.1, 4.9 Hz, 1H), 2.39 (dd, J=10.4, 5.0 Hz, 1H), 2.20-1.85 (m, 3H), 1.02-0.82 (m, 4H); MS (ESI) m/z 275 (M+H)+.

後処理

  1. stirringThe mixture was stirred at ambient temperature for 1 hour
  2. customwas then partitioned between water and ethyl acetate
  3. dry with materialThe organic layer was dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe crude product was purified by chromatography on a 12 g silica gel column
  7. washeluting with 5% ethyl acetate/hexanes for 3 minutes
  8. waita gradient to 100% ethyl acetate over 20 minutes

出典と根拠

ORDレコード
ord-ca23b8f759fd4b1b8bafc20b0976cd8a
出典データセット
uspto-grants-2014_03
特許番号
US08669255B2

反応ノート

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