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

HRID 1362077ノート

反応式

HRID 1362077 の反応式
Br[C:2]1[CH:21]=[N:20][C:5]2[NH:6][C:7](=[O:19])[CH2:8][N:9]([CH2:11][CH2:12][N:13]3[CH2:18][CH2:17][O:16][CH2:15][CH2:14]3)[CH2:10][C:4]=2[CH:3]=1.[C:22]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])(=[O:25])[CH:23]=[CH2:24].C(N(C(C)C)C(C)C)C.CC1C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C>C(#N)CC.CN(C=O)C.CCOCC.CC([O-])=O.CC([O-])=O.[Pd+2]>[C:27]([O:26][C:22](=[O:25])/[CH:23]=[CH:24]/[C:2]1[CH:21]=[N:20][C:5]2[NH:6][C:7](=[O:19])[CH2:8][N:9]([CH2:11][CH2:12][N:13]3[CH2:18][CH2:17][O:16][CH2:15][CH2:14]3)[CH2:10][C:4]=2[CH:3]=1)([CH3:30])([CH3:29])[CH3:28]

参加物

9

反応物 4

HCID 15458tert-Butyl acrylateHCID 80271Tri-o-tolylphosphineHCID 81531DiisopropylethylamineHCID 594569787-Bromo-4-(2-morpholin-4-yl-ethyl)-1,3,4,5-tetrahydro-pyrido[2,3-e][1,4]diazepin-2-one

生成物 1

HCID 59456904(E)-3-[4-(2-Morpholin-4-yl-ethyl)-2-oxo-2,3,4,5-tetrahydro-1H-pyrido[2,3-e][1,4]diazepin-7-yl]acrylic acid tert-butyl ester収率 44%

試薬・触媒・溶媒 4

HCID 167845palladium(II) acetate触媒HCID 3283Diethyl Ether溶媒HCID 6228Dimethylformamide溶媒HCID 7854Propionitrile溶媒

実験手順

A suspension of 7-bromo-4-(2-morpholin-4-yl-ethyl)-1,3,4,5-tetrahydro-pyrido[2,3-e][1,4]diazepin-2-one (0.18 g, 0.52 mmol) in propionitrile (4 mL) and DMF (1 mL) was de-oxygenated with Ar for 15 min. The mixture was treated with tert-butyl acrylate (0.3 mL, 2 mmol) and (i-Pr)2EtN (0.2 mL, 1 mmol) and was de-oxygenated with Ar for 10 min. Pd(OAc)2 (12 mg, 0.053 mmol) and P(o-tol)3 (32 mg, 0.10 mmol) were added simultaneously, and the mixture was de-oxygenated a third time for 5 min. The mixture was heated to reflux overnight, then allowed to cool. The mixture was diluted with Et2O (50 mL) and the resulting solution washed with H2O (20 mL). The organic layer was dried over Na2SO4, filtered and the solvent was removed in vacuo. Purification by flash column chromatography (silica gel, CH2Cl2/MeOH, 97:3) gave the title compound (92 mg, 44%) as an off-white solid: 1H NMR (300 MHz, DMSO-d6) δ 9.51 (s, 1H), 8.52 (s, 1H), 7.61-7.49 (m, 2H), 6.36 (d, J=16.0 Hz, 1H), 4.07 (s, 2H), 3.90 (s, 2H), 3.70-3.67 (m, 4H), 2.78-2.74 (m, 2H), 2.52-2.49 (m, 6H), 1.53 (s, 9H); MS (ESI) m/e 403 (M+H)+.

後処理

  1. waitwas de-oxygenated with Ar for 10 min
  2. customfor 5 min
  3. temperatureThe mixture was heated
  4. temperatureto reflux overnight
  5. temperatureto cool
  6. washthe resulting solution washed with H2O (20 mL)
  7. dry with materialThe organic layer was dried over Na2SO4
  8. filtrationfiltered
  9. customthe solvent was removed in vacuo
  10. customPurification by flash column chromatography (silica gel, CH2Cl2/MeOH, 97:3)

出典と根拠

ORDレコード
ord-2ebbc0fca65c42b2b8ae032d860edf4e
出典データセット
uspto-grants-2011_02
特許番号
US07879872B2

反応ノート

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