Diisopropylethylamine → 3-(7,7-dimethyl-8-oxo-6,7,8,9-tetrahydro-5-oxa-1,9-diaza-benzocyclohepten-3-yl)-N-methyl-N-[1-(R)-(3-methyl-benzofuran-2-yl)-ethyl]acrylamide

HRID 340820ノート

反応式

HRID 340820 の反応式
[CH3:1][N:2]([C@@H:7]([C:9]1[O:10][C:11]2[CH:18]=[CH:17][CH:16]=[CH:15][C:12]=2[C:13]=1[CH3:14])[CH3:8])[C:3](=[O:6])[CH:4]=[CH2:5].Br[C:20]1[CH:33]=[N:32][C:23]2[NH:24][C:25](=[O:31])[C:26]([CH3:30])([CH3:29])[CH2:27][O:28][C:22]=2[CH:21]=1.CCN(C(C)C)C(C)C>C(C#N)C.CN(C=O)C.CC([O-])=O.CC([O-])=O.[Pd+2]>[CH3:29][C:26]1([CH3:30])[C:25](=[O:31])[NH:24][C:23]2[N:32]=[CH:33][C:20]([CH:5]=[CH:4][C:3]([N:2]([CH3:1])[C@@H:7]([C:9]3[O:10][C:11]4[CH:18]=[CH:17][CH:16]=[CH:15][C:12]=4[C:13]=3[CH3:14])[CH3:8])=[O:6])=[CH:21][C:22]=2[O:28][CH2:27]1

参加物

7

反応物 3

HCID 81531DiisopropylethylamineHCID 59332837(R)-N-methyl-N-[1-(3-methyl-benzofuran-2-yl)-ethyl]acrylamideHCID 593328468-bromo-3,3-dimethyl-2,3-dihydropyrido[3,2-b][1,4]oxazepin-4(5H)-one

生成物 1

HCID 684140103-(7,7-dimethyl-8-oxo-6,7,8,9-tetrahydro-5-oxa-1,9-diaza-benzocyclohepten-3-yl)-N-methyl-N-[1-(R)-(3-methyl-benzofuran-2-yl)-ethyl]acrylamide収率 26%

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 suspension of (R)—N-methyl-N-[1-(3-methyl-benzofuran-2-yl)-ethyl]acrylamide (328 mg, 1.35 mmol), 3-bromo-7,7-dimethyl-6,7-dihydro-9H-5-oxa-1,9-diaza-benzocyclohepten-8-one (400 mg, 1.48 mmol), (o-tol)3P (1.32 mg, 0.43 mmol) and DIEA (0.3 mL, 1.6 mmol) in EtCN (10 mL) and DMF (5 mL) was deoxygenated with argon for 30 min. Pd(OAc)2 (50 mg, 0.22 mmol) was added, the mixture was deoxygenated again with argon for 20 min and the mixture was heated to reflux overnight. The mixture was cooled to room temperature and partitinned between EtOAc and water. The residue was suspended in Et2O and then sonicated to give a solid. The solid was collected by filtration. Purification by column chromatography (silica gel, 1:1 hexanes/EtOAc) and sonication in Et2O gave the title compound (150 mg, 26%) as a white solid: 1H NMR (300 MHz, DMSO-d6) δ10.13 (s, 1H), 8.27 (s, 1H), 8.0.1-7.89 (m, 1H), 7.58-7.50 (m, 3H), 7.32-7.18 (m, 3H), 6.19-5.99 (m, 1H), 4.07 (s, 2H), 3.04-2.79 (m, 3H), 248 (s, 3H), 1.64-1.54 (m, 3H), 1.19 (s, 6H); MS (ESI) m/e 434 (M+H)+.

後処理

  1. customwas deoxygenated with argon for 30 min
  2. customthe mixture was deoxygenated again with argon for 20 min
  3. temperaturethe mixture was heated
  4. temperatureto reflux overnight
  5. customsonicated
  6. customto give a solid
  7. filtrationThe solid was collected by filtration
  8. customPurification
  9. customby column chromatography (silica gel, 1:1 hexanes/EtOAc) and sonication in Et2O

出典と根拠

ORDレコード
ord-1b089e6533b84a0bab3d817da869c343
出典データセット
uspto-grants-2014_11
特許番号
US08895545B2

反応ノート

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