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Tri-o-tolylphosphine → (E)-N-methyl-N-(2-methyl-1H-indol-3-ylmethyl)-3-[3-(2-methoxyethyl)-2-oxo-1,2,3,4-tetrahydropyrido[2,3-d]pyrimidin-6-yl]acrylamide

HRID 1690420
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HRID 1690420 반응식
Br[C:2]1[CH:16]=[N:15][C:5]2[NH:6][C:7](=[O:14])[N:8]([CH2:10][CH2:11][O:12][CH3:13])[CH2:9][C:4]=2[CH:3]=1.[CH3:17][C:18]1[NH:19][C:20]2[C:25]([C:26]=1[CH2:27][N:28]([CH3:33])[C:29](=[O:32])[CH:30]=[CH2:31])=[CH:24][CH:23]=[CH:22][CH:21]=2.C1(C)C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C.C(N(C(C)C)CC)(C)C>C(#N)CC.CC([O-])=O.CC([O-])=O.[Pd+2]>[CH3:33][N:28]([CH2:27][C:26]1[C:25]2[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=2)[NH:19][C:18]=1[CH3:17])[C:29](=[O:32])/[CH:30]=[CH:31]/[C:2]1[CH:16]=[N:15][C:5]2[NH:6][C:7](=[O:14])[N:8]([CH2:10][CH2:11][O:12][CH3:13])[CH2:9][C:4]=2[CH:3]=1
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참가 물질

7

반응물 4

HCID 80271Tri-o-tolylphosphineHCID 81531DiisopropylethylamineHCID 221390516-bromo-3-(2-methoxyethyl)-3,4-dihydro-1H-pyrido[2,3-d]pyrimidin-2-oneHCID 22139057N-(2-methyl-1H-indol-3-ylmethyl)-N-methylacrylamide

생성물 1

HCID 11743597(E)-N-methyl-N-(2-methyl-1H-indol-3-ylmethyl)-3-[3-(2-methoxyethyl)-2-oxo-1,2,3,4-tetrahydropyrido[2,3-d]pyrimidin-6-yl]acrylamide
수율 36%

시약·촉매·용매 2

HCID 167845palladium(II) acetate촉매HCID 7854Propionitrile용매

실험 절차

A solution of 6-bromo-3-(2-methoxyethyl)-3,4-dihydro-1H-pyrido[2,3-d]pyrimidin-2-one (0.86 g, 3.00 mmole), N-(2-methyl-1H-indol-3-ylmethyl)-N-methylacrylamide (see Example 1 (a), 0.68 g, 3.00 mmole), Pd(OAc)2 (0.07 g, 0.30 mmole), tri-ortho-tolylphosphine (0.18 g, 0.60 mmole) and diisopropylethylamine (1.31 mL, 7.50 mmole) in propionitrile (50 mL) was deoxygenated, then was heated at reflux under N2 overnight. The dark mixture was filtered through a pad of Celite®, and the filter pad was rinsed with acetonitrile (250 mL). The filtrate was concentrated in vacuo, and the residue was purified by flash chromatography on silica gel (10% EtOAc/EtOH). The title compound (0.46 g, 36%) was obtained as a light yellow solid after drying in vacuo: MS (ES) m/e 434 (M+H)+.

후처리

  1. temperaturewas heated
  2. temperatureat reflux under N2 overnight
  3. filtrationThe dark mixture was filtered through a pad of Celite®
  4. washthe filter pad was rinsed with acetonitrile (250 mL)
  5. concentrationThe filtrate was concentrated in vacuo
  6. customthe residue was purified by flash chromatography on silica gel (10% EtOAc/EtOH)

출처 및 근거

ORD 기록
ord-34645134f8b241d9958f0b47dd607551
출처 데이터셋
uspto-grants-2012_04
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08153652B2

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