Ethyl Acetate → 6-(2-(4,4,4-trifluorobutyl)-2,3,4,5-tetrahydro-1H-benzo[c]azepin-7-yloxy)nicotinamide

HRID 228380ノート

反応式

HRID 228380 の反応式
[CH2:1]1[C:7]2[CH:8]=[CH:9][C:10]([O:12][C:13]3[CH:21]=[CH:20][C:16]([C:17]([NH2:19])=[O:18])=[CH:15][N:14]=3)=[CH:11][C:6]=2[CH2:5][CH2:4][CH2:3][NH:2]1.C([O-])([O-])=O.[K+].[K+].Br[CH2:29][CH2:30][CH2:31][C:32]([F:35])([F:34])[F:33].C(OCC)(=O)C>CN(C=O)C>[F:33][C:32]([F:35])([F:34])[CH2:31][CH2:30][CH2:29][N:2]1[CH2:3][CH2:4][CH2:5][C:6]2[CH:11]=[C:10]([O:12][C:13]3[CH:21]=[CH:20][C:16]([C:17]([NH2:19])=[O:18])=[CH:15][N:14]=3)[CH:9]=[CH:8][C:7]=2[CH2:1]1

参加物

6

反応物 4

HCID 8857Ethyl AcetateHCID 11430Potassium CarbonateHCID 5210064-Bromo-1,1,1-trifluorobutaneHCID 597302166-(2,3,4,5-tetrahydro-1H-benzo[c]azepin-7-yloxy)nicotinamide

生成物 1

HCID 444340856-(2-(4,4,4-trifluorobutyl)-2,3,4,5-tetrahydro-1H-benzo[c]azepin-7-yloxy)nicotinamide

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

反応条件

温度
95 °C

実験手順

Mix 6-(2,3,4,5-tetrahydro-1H-benzo[c]azepin-7-yloxy)nicotinamide (Example 447, Part E, 0.350 g, 1.24 mmol), K2CO3 (0.427 g, 3.09 mmol), and 4-bromo-1,1,1-trifluorobutane (0.248 g, 1.30 mmol) in DMF (6.2 mL). Heat at 95° C. for 5.5 hours, then at 50° C. overnight. Cool the reaction mixture to room temperature and add ethyl acetate (100 mL). Wash with water (1×30 mL) and brine (1×30 mL). Dry the organic layer over Na2SO4, filter and concentrate. Purify by flash chromatography eluting with 6% to 20% (2.0 M NH3 in methanol) in ethyl acetate to give the title compound: MS ES+ 394.2 (M+H)+, HRMS calcd for C20H23N3O2F3 394.1742 (M+H)+, found 394.1733, time 0.53 min; HPLC [YMC-Pro pack C-18 (150×4.6 mm, S-5 microm), 0.05% TEA/acetonitrile in 0.05% TFA/water at 1.0 mL/min, 10-20% over 5 min, 20-95% over 18 min], tR=10.1 min, 100% purity.

後処理

  1. customat 50° C.
  2. customovernight
  3. temperatureCool the reaction mixture to room temperature
  4. washWash with water (1×30 mL) and brine (1×30 mL)
  5. dry with materialDry the organic layer over Na2SO4
  6. filtrationfilter
  7. concentrationconcentrate
  8. customPurify by flash chromatography
  9. washeluting with 6% to 20% (2.0 M NH3 in methanol) in ethyl acetate

出典と根拠

ORDレコード
ord-683418860e14428b81a9373a33e319a4
出典データセット
uspto-grants-2009_07
特許番号
US07560463B2

反応ノート

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