Tri-o-tolylphosphine → (E)-3-(2,2-Dimethyl-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-7-yl)-N-methyl-N-(3-methylbenzofuran-2-ylmethyl)acrylamide

HRID 2097084노트

반응식

HRID 2097084 반응식
[CH3:1][N:2]([CH2:7][C:8]1[O:9][C:10]2[CH:17]=[CH:16][CH:15]=[CH:14][C:11]=2[C:12]=1[CH3:13])[C:3](=[O:6])[CH:4]=[CH2:5].C(N(C(C)C)CC)(C)C.Br[C:28]1[CH:37]=[N:36][C:35]2[NH:34][CH2:33][C:32]([CH3:39])([CH3:38])[O:31][C:30]=2[CH:29]=1.CC1C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C>C(#N)CC.CN(C=O)C.CC([O-])=O.CC([O-])=O.[Pd+2].C(Cl)Cl.CO>[CH3:38][C:32]1([CH3:39])[O:31][C:30]2[CH:29]=[C:28](/[CH:5]=[CH:4]/[C:3]([N:2]([CH3:1])[CH2:7][C:8]3[O:9][C:10]4[CH:17]=[CH:16][CH:15]=[CH:14][C:11]=4[C:12]=3[CH3:13])=[O:6])[CH:37]=[N:36][C:35]=2[NH:34][CH2:33]1

참가 물질

9

반응물 4

HCID 80271Tri-o-tolylphosphineHCID 81531DiisopropylethylamineHCID 57742103N-methyl-N-(3-methylbenzofuran-2-ylmethyl)acrylamideHCID 592775797-bromo-2,2-dimethyl-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazine

생성물 1

HCID 16659991(E)-3-(2,2-Dimethyl-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-7-yl)-N-methyl-N-(3-methylbenzofuran-2-ylmethyl)acrylamide수율 59%

시약·촉매·용매 4

HCID 167845palladium(II) acetate촉매HCID 6228Dimethylformamide용매HCID 7854Propionitrile용매HCID 21226129Dichloromethane methanol용매

실험 절차

A solution of N-methyl-N-(3-methylbenzofuran-2-ylmethyl)acrylamide (0.190 g, 0.637 mmol) in propionitrile (3 mL) and DMF (0.6 mL) was deoxygenated with Ar for 20 min. The solution was treated with diisopropylethylamine (0.23 mL, 1.33 mmol) and 7-bromo-2,2-dimethyl-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazine (0.154 g, 0.828 mmol). The solution was deoxygenated with Ar for 20 min. Pd(OAc)2 (0.014 g, 0.063 mmol) and P(o-tol)3 (0.038 g, 0.12 mmol) were then added and the solution was deoxygenated again with Ar for 10 min. The mixture was heated to reflux for 2 h, then allowed to cool. The mixture was diluted with H2O (200 mL) and the solution was washed with EtOAc (3×50 mL). The combined organic layers were washed with brine (2×30 mL), dried (Na2SO4) and concentrated to give a dark green oil. Column chromatography (silica gel, CH2Cl2/MeOH, 100 to 98:2) gave the title compound (0.14 g, 59%) as a light yellow solid and as a mixture of amide rotamers: 1H NMR (500 MHz, DMSO-d6) δ 7.79 (s, 1H), 7.56-7.54 (m, 1H), 7.51-7.47 (m, 2H), 7.41-7.38 (m, 1H), 7.32 (br s, 1H), 7.29-6.93 (m, 3H), 4.95-4.76 (m, 2H), 3.19 (m, 2H), 3.14-2.90 (m, 3H), 2.25 (s, 3H), 1.26 (s, 6H); MS (ESI) m/e 392 (M+H)+.

후처리

  1. customThe solution was deoxygenated with Ar for 20 min
  2. customthe solution was deoxygenated again with Ar for 10 min
  3. temperatureThe mixture was heated
  4. temperatureto reflux for 2 h
  5. temperatureto cool
  6. additionThe mixture was diluted with H2O (200 mL)
  7. washthe solution was washed with EtOAc (3×50 mL)
  8. washThe combined organic layers were washed with brine (2×30 mL)
  9. dry with materialdried (Na2SO4)
  10. concentrationconcentrated
  11. customto give a dark green oil

출처 및 근거

ORD 기록
ord-b81c45629c0e49e68e9b3b77d705cb0c
출처 데이터셋
uspto-grants-2013_05
특허 번호
US08450307B2

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