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

HRID 1362339ノート

反応式

HRID 1362339 の反応式
[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](C)(C)[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]>[O:31]1[CH2:32][CH2:33][NH:34][C:35]2[N:36]=[CH:37][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:29][C:30]1=2

参加物

8

反応物 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

生成物 1

HCID 16660142(E)-3-(3,4-Dihydro-2H-pyrido[3,2-b][1,4]oxazin-7-yl)-N-methyl-N-(3-methylbenzofuran-2-ylmethyl)acrylamide収率 52%

試薬・触媒・溶媒 3

HCID 167845palladium(II) acetate触媒HCID 6228Dimethylformamide溶媒HCID 7854Propionitrile溶媒

実験手順

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 (0.34 mL, 1.97 mmol) and 7-bromo-2,2-dimethyl-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazine (0.188 g, 0.828 mmol). The solution was deoxygenated with Ar for 20 min. Pd(OAc)2 (0.014 g, 0.078 mmol) and P(o-tol)3 (0.038 g, 0.15 mmol) were then added and the solution was deoxygenated again with Ar for 20 min. The mixture was heated to reflux for 2 h, then allowed to cool. The mixture was diluted with H2O (200 mL) and the resulting solution was washed with EtOAc (3×50 mL). The combined organic layers were washed with brine (2×30 mL), dried (Na2SO4) and concentrated to a dark green oil. Column chromatography (silica gel, CH2Cl2/MeOH, 100 to 98:2) gave the title compound (0.12 g, 52%) as a light yellow solid and as a mixture of amide rotamers: 1H NMR (300 MHz, DMSO-d6) δ 7.83 (br s, 1H), 7.62-7.60 (m, 1H), 7.56-7.51 (m, 2H), 7.48-7.41 (m, 1H), 7.38-7.69 (m, 4H), 5.01-4.95 (m, 2H), 4.03 (s, 2H), 3.48 (s, 2H), 3.06-2.90 (m, 3H), 2.18 (s, 3H); MS (ESI) m/e 364 (M+H)+.

後処理

  1. customThe solution was deoxygenated with Ar for 20 min
  2. customthe solution was deoxygenated again with Ar for 20 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 resulting 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 to a dark green oil

出典と根拠

ORDレコード
ord-1546a3dac2454018b396bb2bd1b800dd
出典データセット
uspto-grants-2011_02
特許番号
US07879872B2

反応ノート

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