Hydrazine → N-((1S)-2-amino-1-{[2-(trifluoromethyl)phenyl]methyl}ethyl)-4-(4-bromo-1-ethyl-1H-pyrazol-5-yl)-2-thiophenecarboxamide

HRID 1845432ノート

反応式

HRID 1845432 の反応式
[Br:1][C:2]1[CH:3]=[N:4][N:5]([CH2:39][CH3:40])[C:6]=1[C:7]1[CH:8]=[C:9]([C:12]([NH:14][C@@H:15]([CH2:28][C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=2[C:35]([F:38])([F:37])[F:36])[CH2:16][N:17]2C(=O)C3C(=CC=CC=3)C2=O)=[O:13])[S:10][CH:11]=1.NN>CO>[NH2:17][CH2:16][C@@H:15]([NH:14][C:12]([C:9]1[S:10][CH:11]=[C:7]([C:6]2[N:5]([CH2:39][CH3:40])[N:4]=[CH:3][C:2]=2[Br:1])[CH:8]=1)=[O:13])[CH2:28][C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=1[C:35]([F:38])([F:37])[F:36]

参加物

4

反応物 2

HCID 9321HydrazineHCID 578264464-(4-bromo-1-ethyl-1H-pyrazol-5-yl)-N-((1S)-2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-1-{[2-(trifluoromethyl)phenyl]methyl}ethyl)-2-thiophenecarboxamide

生成物 1

HCID 24996913N-((1S)-2-amino-1-{[2-(trifluoromethyl)phenyl]methyl}ethyl)-4-(4-bromo-1-ethyl-1H-pyrazol-5-yl)-2-thiophenecarboxamide収率 73.6%

試薬・触媒・溶媒 1

HCID 887Methanol溶媒

実験手順

4-(4-bromo-1-ethyl-1H-pyrazol-5-yl)-N-((1S)-2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-1-{[2-(trifluoromethyl)phenyl]methyl}ethyl)-2-thiophenecarboxamide (250 mg, 0.39 mmol) was dissolved in MeOH (5 mL) and treated with NH2NH2 (0.5 mL, 15.93 mmol). The mixture was stirred at RT overnight, and concentrated. The residue was purified by column chromatography [silica, 2-10% MeOH in CHCl3 (0.5% NH4OH)]affording the free base of the title compound, which was treated with HCl(aq) in MeOH to give the title compound (144 mg, 51%) as an off white solid: LC-MS (ES) m/z 502 (M+H)+. 1H NMR (d4-MeOD, 400 MHz) δ ppm 7.93-7.87 (m, 2H), 7.72 (d, J=8.1 Hz, 1H), 7.62 (s, 1H), 7.57-7.51 (m, 2H), 7.43 (t, J=6.6 Hz, 1H), 4.67 (m, 1H), 4.25 (q, J=7.3 Hz, 2H), 3.37-3.11 (m, 4H), and 1.37 (t, J=7.1 Hz, 3H).

後処理

  1. concentrationconcentrated
  2. customThe residue was purified by column chromatography [silica, 2-10% MeOH in CHCl3 (0.5% NH4OH)
  3. additionwas treated with HCl(aq) in MeOH

出典と根拠

ORDレコード
ord-07819180d83e438a907300f3716b3d03
出典データセット
uspto-grants-2015_02
特許番号
US08946278B2

反応ノート

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