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 1362077노트

반응식

HRID 1362077 반응식
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]

참가 물질

9

반응물 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

생성물 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 ester수율 44%

시약·촉매·용매 4

HCID 167845palladium(II) acetate촉매HCID 3283Diethyl Ether용매HCID 6228Dimethylformamide용매HCID 7854Propionitrile용매

실험 절차

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)+.

후처리

  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)

출처 및 근거

ORD 기록
ord-2ebbc0fca65c42b2b8ae032d860edf4e
출처 데이터셋
uspto-grants-2011_02
특허 번호
US07879872B2

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