Diisopropylethylamine → HCID 44253062、化合物

HRID 19163ノート

反応式

HRID 19163 の反応式
[F:1][C:2]1[C:22]([C:23]([OH:26])([CH3:25])[CH3:24])=[CH:21][CH:20]=[CH:19][C:3]=1[O:4][C:5]1[CH2:9][N:8]([C@@H:10]([CH2:14][CH:15]([CH3:17])[CH3:16])[C:11](O)=[O:12])[C:7](=[O:18])[CH:6]=1.[CH3:27][N:28]1[CH:32]=[CH:31][C:30]([NH2:33])=[N:29]1.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.C(N(CC)C(C)C)(C)C>ClCCl>[CH3:27][N:28]1[CH:32]=[CH:31][C:30]([NH:33][C:11](=[O:12])[C@@H:10]([N:8]2[CH2:9][C:5]([O:4][C:3]3[CH:19]=[CH:20][CH:21]=[C:22]([C:23]([OH:26])([CH3:24])[CH3:25])[C:2]=3[F:1])=[CH:6][C:7]2=[O:18])[CH2:14][CH:15]([CH3:16])[CH3:17])=[N:29]1

参加物

6

反応物 4

HCID 81531DiisopropylethylamineHCID 1372541-Methyl-3-aminopyrazoleHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 66899241(S)-2-{4-[2-fluoro-3-(1-hydroxy-1-methyl-ethyl)-phenoxy]-2-oxo-2,5-dihydro-pyrrol-1-yl}-4-methyl-pentanoic acid

生成物 1

HCID 44253062HCID 44253062、化合物収率 92.7%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

反応条件

温度
0 °C

実験手順

To a solution of (S)-2-{4-[2-fluoro-3-(1-hydroxy-1-methyl-ethyl)-phenoxy]-2-oxo-2,5-dihydro-pyrrol-1-yl}-4-methyl-pentanoic acid (0.392 g, 1.07 mmol) in dichloromethane (10 mL) was added 1-methyl-1H-pyrazol-3-ylamine (0.208 g, 2.14 mmol) and benzotriazol-1-yl-oxy-tris(dimethylamino)phosphonium hexafluorophosphate (0.522 g, 1.18 mmol). The mixture was stirred at 0° C. and N,N-diisopropylethylamine (0.304 g, 2.35 mmol) was added. The mixture was stirred at room temperature overnight and the solvents were evaporated. The residue was treated with ethyl acetate and ammonium chloride solution, and the organic layer separated. The organic layer was washed with brine and dried over sodium sulfate. The solvents were evaporated and the residue was purified by ISCO flash chromatography (Teledyne Isco RediSep Flash Column 112 g, 60% to 100% ethyl acetate/hexanes) which afforded (S)-2-{4-[2-fluoro-3-(1-hydroxy-1-methyl-ethyl)-phenoxy]-2-oxo-2,5-dihydro-pyrrol-1-yl}-4-methyl-pentanoic acid (1-methyl-1H-pyrazol-3-yl)-amide (0.441 g, 92%) as an off-white solid: HR-ES-MS m/z calculated for C23H29FN4O4 [M+H]+ 445.2246, observed 445.2246, 1H NMR (300 MHz, DMSO-d6) δ 1.00 0.90 (d, J=6.4 Hz, 3H), 0.93 (d, J=6.4 Hz, 3H), 1.36-1.47 (m, 1H), 1.49 (s, 6H), 1.52-1.65 (m, 1H), 1.67-1.82 (m, 1H), 3.73 (s, 3H), 4.20 (d, J=18.4 Hz, 1H), 4.58 (d, J=18.4 Hz, 1H), 4.81 (s, 1H), 4.88 (dd, J=10.7, 5.0 Hz, 1H), 5.42 (s, 1H), 6.40 (d, J=2.1 Hz, 1H), 7.23 (t, J=7.8 Hz, 1H), 7.29-7.40 (m, 1H), 7.54 (d, J=2.1 Hz, 1H), 7.51-7.60 (m, 1H), 10.73 (s, 1H).

後処理

  1. stirringThe mixture was stirred at room temperature overnight
  2. customthe solvents were evaporated
  3. additionThe residue was treated with ethyl acetate and ammonium chloride solution
  4. customthe organic layer separated
  5. washThe organic layer was washed with brine
  6. dry with materialdried over sodium sulfate
  7. customThe solvents were evaporated
  8. customthe residue was purified by ISCO flash chromatography (Teledyne Isco RediSep Flash Column 112 g, 60% to 100% ethyl acetate/hexanes) which

出典と根拠

ORDレコード
ord-1c7673fd26384ae4b0845a0c38866170
出典データセット
uspto-grants-2010_06
特許番号
US07741327B2

反応ノート

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