tert-Butyl acrylate → 3-(3-Oxo-2,3,4,5-tetrahydro-1H-pyrido[2,3-e][1,4]diazepin-7-yl)-acrylic acid tert-butyl ester

HRID 2097108ノート

反応式

HRID 2097108 の反応式
Br[C:2]1[CH:13]=[N:12][C:5]2[NH:6][CH2:7][C:8](=[O:11])[NH:9][CH2:10][C:4]=2[CH:3]=1.[C:14]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])(=[O:17])[CH:15]=[CH2:16].C(N(C(C)C)CC)(C)C>CN(C=O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[C:19]([O:18][C:14](=[O:17])[CH:15]=[CH:16][C:2]1[CH:13]=[N:12][C:5]2[NH:6][CH2:7][C:8](=[O:11])[NH:9][CH2:10][C:4]=2[CH:3]=1)([CH3:22])([CH3:21])[CH3:20]

参加物

6

反応物 3

HCID 15458tert-Butyl acrylateHCID 81531DiisopropylethylamineHCID 592776207-Bromo-1,2,4,5-tetrahydro-pyrido[2,3-e][1,4]diazepin-3-one

生成物 1

HCID 669672043-(3-Oxo-2,3,4,5-tetrahydro-1H-pyrido[2,3-e][1,4]diazepin-7-yl)-acrylic acid tert-butyl ester収率 55.3%

試薬・触媒・溶媒 2

HCID 167845palladium(II) acetate触媒HCID 6228Dimethylformamide溶媒

反応条件

温度
90 °C

実験手順

7-Bromo-1,2,4,5-tetrahydro-pyrido[2,3-e][1,4]diazepin-3-one (145 mg, 0.6 mmol) and tert-butyl acrylate (307 mg, 2.4 mmol) were dissolved in DMF (3 mL) and the reaction vessel was purged with argon for 5 min. Tri-σ-tolylphosphine (37 mg, 0.12 mmol) and palladium acetate (14 mg, 0.06 mmol) were added and the solution was degassed with argon. Diisopropylethylamine (0.23 mL, 1.32 mmol) was added and the solution was degassed with argon, sealed and heated to 90° C. for 16 h. The reaction was cooled to room temperature and filtered through a bed of celite. The filter cake was washed with ethyl acetate (50 mL) and the filtrate was washed with H2O (5 mL) and brine (5 mL), dried over MgSO4 and concentrated to a brown oil. The oil was subjected to silica gel chromatography (5% MeOH/CH2Cl2 to 10% MeOH/CH2Cl2) to yield the title compound as a yellow solid (96 mg, 52%). 1H NMR (300 MHz, DMSO-d6) 8.18 (t, J=5.7 Hz, 1H), 8.07 (d, J=2.1 Hz, 1H), 7.37 (d, J=15.8 Hz, 1H), 7.35 (t, J=5.3 Hz, 1H), 6.24 (d, J=15.8 Hz, 1H), 4.28 (d, J=5.7 Hz, 2H), 3.98 (d, J=5.1 Hz, 2H), 1.45 (s, 9H); ESI MS m/z 290 [C15H19N3O3+H]+.

後処理

  1. customthe reaction vessel was purged with argon for 5 min
  2. customthe solution was degassed with argon
  3. customthe solution was degassed with argon
  4. customsealed
  5. temperatureThe reaction was cooled to room temperature
  6. filtrationfiltered through a bed of celite
  7. washThe filter cake was washed with ethyl acetate (50 mL)
  8. washthe filtrate was washed with H2O (5 mL) and brine (5 mL)
  9. dry with materialdried over MgSO4
  10. concentrationconcentrated to a brown oil

出典と根拠

ORDレコード
ord-cffe0cac2d2844359c2f5b1157312694
出典データセット
uspto-grants-2013_05
特許番号
US08450307B2

反応ノート

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