Tri-o-tolylphosphine → (E)-7-{2-[Methyl-(3-methylbenzofuran-2-ylmethyl)carbamoyl]vinyl}-1,2,3,5-tetrahydro-pyrido[2,3-e][1,4]diazepine-4-carboxylic acid tert-butyl ester

HRID 1879971ノート

反応式

HRID 1879971 の反応式
[C:1]([O:5][C:6]([N:8]1[CH2:14][C:13]2[CH:15]=[C:16](Br)[CH:17]=[N:18][C:12]=2[NH:11][CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:20][N:21]([CH2:26][C:27]1[O:28][C:29]2[CH:36]=[CH:35][CH:34]=[CH:33][C:30]=2[C:31]=1[CH3:32])[C:22](=[O:25])[CH:23]=[CH2:24].C(N(C(C)C)C(C)C)C.CC1C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C>C(#N)CC.CN(C=O)C.CCOC(C)=O.CC([O-])=O.CC([O-])=O.[Pd+2]>[C:1]([O:5][C:6]([N:8]1[CH2:14][C:13]2[CH:15]=[C:16](/[CH:24]=[CH:23]/[C:22](=[O:25])[N:21]([CH3:20])[CH2:26][C:27]3[O:28][C:29]4[CH:36]=[CH:35][CH:34]=[CH:33][C:30]=4[C:31]=3[CH3:32])[CH:17]=[N:18][C:12]=2[NH:11][CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

参加物

9

反応物 4

HCID 80271Tri-o-tolylphosphineHCID 81531DiisopropylethylamineHCID 57742103N-methyl-N-(3-methylbenzofuran-2-ylmethyl)acrylamideHCID 593328327-Bromo-1,2,3,5-tetrahydro-pyrido[2,3-e][1,4]diazepine-4-carboxylic acid tert-butyl ester

生成物 1

HCID 24891455(E)-7-{2-[Methyl-(3-methylbenzofuran-2-ylmethyl)carbamoyl]vinyl}-1,2,3,5-tetrahydro-pyrido[2,3-e][1,4]diazepine-4-carboxylic acid tert-butyl ester収率 63%

試薬・触媒・溶媒 4

HCID 167845palladium(II) acetate触媒HCID 6228Dimethylformamide溶媒HCID 7854Propionitrile溶媒HCID 8857Ethyl Acetate溶媒

実験手順

A solution of 7-bromo-1,2,3,5-tetrahydro-pyrido[2,3-e][1,4]diazepine-4-carboxylic acid tert-butyl ester (0.53 g, 1.6 mmol) and N-methyl-N-(3-methylbenzofuran-2-ylmethyl)acrylamide (0.41 g, 1.8 mmol) in propionitrile (8.0 mL) and DMF (2.0 mL) was de-oxygenated with Ar for 10 min. The mixture was treated with (i-Pr)2EtN (0.62 mL, 3.5 mmol) and was de-oxygenated with Ar for 5 min. Pd(OAc)2 (36 mg, 0.16 mmol) and P(o-tol)3 (100 mg, 0.33 mmol) were added simultaneously, and the mixture was de-oxygenated a third time for 10 min. The mixture was heated to reflux for 6 h, then allowed to cool. The mixture was diluted with EtOAc (100 mL) and washed with H2O (50 mL). The organic layer was dried over Na2SO4, filtered and concentrated to an orange oil. Purification by flash column chromatography (silica gel, CH2Cl2/MeOH, 98:2) gave the title compound (0.48 g, 62%) as a white powder and as a mixture of amide rotamers: 1H NMR (300 MHz, DMSO-d6) δ 8.15-8.10 (m, 1H), 7.87-7.74 (m, 1H), 7.57-7.42 (m, 3H), 7.32-6.77 (m, 4H), 4.97-4.78 (m, 2H), 4.51-4.42 (m, 2H), 3.59-3.57 (m, 2H), 3.43-3.41 (m, 2H), 3.17-2.92 (m, 3H), 2.26 (s, 3H), 1.38-1.24 (m, 9H); MS (ESI) m/e 477 (M+H)+.

後処理

  1. customfor 10 min
  2. temperatureThe mixture was heated
  3. temperatureto reflux for 6 h
  4. temperatureto cool
  5. washwashed with H2O (50 mL)
  6. dry with materialThe organic layer was dried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated to an orange oil
  9. customPurification by flash column chromatography (silica gel, CH2Cl2/MeOH, 98:2)

出典と根拠

ORDレコード
ord-be008058cf90447e9708683469969583
出典データセット
uspto-grants-2012_11
特許番号
US08318720B2

反応ノート

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