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

HRID 1362089
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HRID 1362089 반응식
Br[C:2]1[CH:22]=[N:21][C:5]2[NH:6][C:7](=[O:20])[CH2:8][N:9]([CH2:11][CH2:12][CH2:13][N:14]3[CH2:19][CH2:18][O:17][CH2:16][CH2:15]3)[CH2:10][C:4]=2[CH:3]=1.[C:23]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])(=[O:26])[CH:24]=[CH2:25].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:28]([O:27][C:23](=[O:26])/[CH:24]=[CH:25]/[C:2]1[CH:22]=[N:21][C:5]2[NH:6][C:7](=[O:20])[CH2:8][N:9]([CH2:11][CH2:12][CH2:13][N:14]3[CH2:19][CH2:18][O:17][CH2:16][CH2:15]3)[CH2:10][C:4]=2[CH:3]=1)([CH3:31])([CH3:30])[CH3:29]
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참가 물질

9

반응물 4

HCID 15458tert-Butyl acrylateHCID 80271Tri-o-tolylphosphineHCID 81531DiisopropylethylamineHCID 594569707-Bromo-4-(3-morpholin-4-yl-propyl)-1,3,4,5-tetrahydro-pyrido[2,3-e][1,4]diazepin-2-one

생성물 1

HCID 59456935(E)-3-[4-(3-Morpholin-4-yl-propyl)-2-oxo-2,3,4,5-tetrahydro-1H-pyrido[2,3-e][1,4]diazepin-7-yl]acrylic acid tert-butyl ester수율 55%

시약·촉매·용매 4

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

실험 절차

A suspension of 7-bromo-4-(3-morpholin-4-yl-propyl)-1,3,4,5-tetrahydro-pyrido[2,3-e][1,4]diazepin-2-one (5.70 g, 15.4 mmol) in propionitrile (120 mL) and DMF (30 mL) was de-oxygenated with Ar for 15 min. The mixture was treated with tert-butyl acrylate (9.0 mL, 61 mmol) and (i-Pr)2EtN (5.7 mL, 33 mmol) and was de-oxygenated with Ar for 10 min. Pd(OAc)2 (0.35 g, 1.6 mmol) and P(o-tol)3 (0.94 g, 3.1 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 (200 mL). The organic solution was filtered through Celite, washed with H2O (200 mL), dried over Na2SO4, filtered and then concentrated in vacuo. Purification by flash column chromatography (silica gel, CH2Cl2/MeOH, 97:3 to 96:4) gave the title compound (3.49 g, 55%) as a tan solid: MS (ESI) m/e 417 (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. filtrationThe organic solution was filtered through Celite
  7. washwashed with H2O (200 mL)
  8. dry with materialdried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customPurification by flash column chromatography (silica gel, CH2Cl2/MeOH, 97:3 to 96:4)

출처 및 근거

ORD 기록
ord-cd01d18806ed4f2f9384f65e99f88456
출처 데이터셋
uspto-grants-2011_02
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US07879872B2

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