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

HRID 340822
ノート
印刷プレビュー

反応式

HRID 340822 の反応式
Br[C:2]1[CH:14]=[N:13][C:5]2[NH:6][CH2:7][C:8]([CH3:12])([CH3:11])[N:9]=[CH:10][C:4]=2[CH:3]=1.[CH3:15][N:16]([CH2:21][C:22]1[O:23][C:24]2[CH:31]=[CH:30][CH:29]=[CH:28][C:25]=2[C:26]=1[CH3:27])[C:17](=[O:20])[CH:18]=[CH2:19].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]>[CH3:11][C:8]1([CH3:12])[CH2:7][NH:6][C:5]2[N:13]=[CH:14][C:2](/[CH:19]=[CH:18]/[C:17]([N:16]([CH3:15])[CH2:21][C:22]3[O:23][C:24]4[CH:31]=[CH:30][CH:29]=[CH:28][C:25]=4[C:26]=3[CH3:27])=[O:20])=[CH:3][C:4]=2[CH:10]=[N:9]1
参加物実験手順後処理出典と根拠反応ノート

参加物

9

反応物 4

HCID 80271Tri-o-tolylphosphineHCID 81531DiisopropylethylamineHCID 57742103N-methyl-N-(3-methylbenzofuran-2-ylmethyl)acrylamideHCID 593328417-Bromo-3,3-dimethyl-2,3-dihydro-1H-pyrido[2,3-e][1,4]diazepine

生成物 1

HCID 59332851(E)-3-(3,3-Dimethyl-2,3-dihydro-1H-pyrido[2,3-e][1,4]diazepin-7-yl)-N-methyl-N-(3-methylbenzofuran-2-ylmethyl)acrylamide収率 21.1%

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 suspension of 7-bromo-3,3-dimethyl-2,3-dihydro-1H-pyrido[2,3-e][1,4]diazepine (255 mg, 1.00 mmol) and N-methyl-N-(3-methylbenzofuran-2-ylmethyl)acrylamide (0.28 g, 1.2 mmol) in propionitrile (5.0 mL) and DMF (1.3 mL) was de-oxygenated with Ar for 10 min. The mixture was treated with (i-Pr)2EtN (0.38 mL, 2.2 mmol) and was de-oxygenated with Ar for 5 min. Pd(OAc)2 (22 mg, 0.10 mmol) and P(o-tol)3 (63 mg, 0.21 mmol) were added simultaneously, and the mixture was de-oxygenated a third time for 5 min. The mixture was heated to reflux overnight, then allowed to cool. The mixture was diluted with EtOAc (50 mL) and washed with H2O (25 mL). The organic layer was dried over Na2SO4, filtered and concentrated to an orange oil. Purification by flash column chromatography (silica gel, CH2Cl2/MeOH, 96:4) followed by trituration with Et2O gave the title compound (85 mg, 21%) as a yellow powder and as a mixture of amide rotamers: 1H NMR (300 MHz, DMSO-d6) δ8.44-8.43 (m, 1H), 8.25 (s, 1H), 8.19-8.15 (m, 1H), 8.06 (s, 1H), 7.58-7.08 (m, 6H), 4.99-4.79 (m, 2H), 3.18-2.92 (m, 5H), 2.27 (s, 3H), 1.16 (s, 6H); MS (ESI) m/e 403 (M+H)+.

後処理

  1. waitwas de-oxygenated with Ar for 5 min
  2. customfor 5 min
  3. temperatureThe mixture was heated
  4. temperatureto reflux overnight
  5. temperatureto cool
  6. washwashed with H2O (25 mL)
  7. dry with materialThe organic layer was dried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated to an orange oil
  10. customPurification by flash column chromatography (silica gel, CH2Cl2/MeOH, 96:4)

出典と根拠

ORDレコード
ord-2afcea014e614d239a0018d283c1231b
出典データセット
uspto-grants-2014_11
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08895545B2

反応ノート

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