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

HRID 225937노트

반응식

HRID 225937 반응식
[CH3:1][N:2]([CH2:7][C:8]1[N:9]([CH3:17])[C:10]2[C:15]([CH:16]=1)=[CH:14][CH:13]=[CH:12][CH:11]=2)[C:3](=[O:6])[CH:4]=[CH2:5].Br[C:19]1[CH:29]=[N:28][C:22]2[NH:23][C:24](=[O:27])[O:25][CH2:26][C:21]=2[CH:20]=1.CCN(C(C)C)C(C)C.C1(C)C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C>C(#N)CC.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:1][N:2]([CH2:7][C:8]1[N:9]([CH3:17])[C:10]2[C:15]([CH:16]=1)=[CH:14][CH:13]=[CH:12][CH:11]=2)[C:3](=[O:6])/[CH:4]=[CH:5]/[C:19]1[CH:29]=[N:28][C:22]2[NH:23][C:24](=[O:27])[O:25][CH2:26][C:21]=2[CH:20]=1

참가 물질

7

반응물 4

HCID 80271Tri-o-tolylphosphineHCID 81531DiisopropylethylamineHCID 159259906-bromo-1H,2H,4H-pyrido(2,3-d)(1,3)oxazin-2-oneHCID 20752825N-Methyl-N-[(1-methyl-2-indolyl)methyl]acrylamide

생성물 1

HCID 9821027(E)-N-methyl-N-(1-methyl-1H-indol-2-ylmethyl)-3-(2-oxo-1,4-dihydro-2H-pyrido[2,3-d]-1,3-oxazin-6yl)acrylamide수율 55.3%

시약·촉매·용매 2

HCID 167845palladium(II) acetate촉매HCID 7854Propionitrile용매

실험 절차

To a stirred solution of N-methyl-N-(1-methyl-1H-indol-2-ylmethyl)acrylamide (1.19 g, 5.2 mmole) in propionitrile (50 mL) was added 6-bromo-2-oxo-1,4-dihydro-2H-pyrido[2,3-d]-1,3-oxazine (1.1 g, 4.9 mmole), DIEA (1.75 mL, 10 mmole), palladium(II) acetate (112 mg, 0.5 mmole), and tri-o-tolylphosphine (304 mg, 1.0 mmole). The reaction was purged with argon and heated at reflux for 16 hr, then was cooled to RT and concentrated under vacuum. The residue was taken up in CHCl3 and the solution was filtered through a pad of silica gel (3% methanol/CHCl3). The filtrate was concentrated and the residue was triturated with ethyl acetate, collected by suction filtration, and dried under vacuum gave the title compound (1.02 g, 55%) as an off-white solid: LCMS (ES) m/e 377 4 (M+H)+.

후처리

  1. customThe reaction was purged with argon
  2. temperatureheated
  3. temperatureat reflux for 16 hr
  4. concentrationconcentrated under vacuum
  5. filtrationthe solution was filtered through a pad of silica gel (3% methanol/CHCl3)
  6. concentrationThe filtrate was concentrated
  7. customthe residue was triturated with ethyl acetate
  8. filtrationcollected by suction filtration
  9. customdried under vacuum

출처 및 근거

ORD 기록
ord-68de3b63945347abbf8dde52864f6a2c
출처 데이터셋
uspto-grants-2009_07
특허 번호
US07557125B2

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