Triethylamine → 4-(2-Cyclopropanesulfonylamino-2-phenyl-acetyl)-morpholine-3-carboxylic acid {4-[3-(5-chloro-2-hydroxy-phenyl)-1-methyl-1H-pyrazol-4-ylethynyl]-phenyl}-amide

HRID 2075780ノート

反応式

HRID 2075780 の反応式
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([OH:41])=[C:6]([C:8]2[C:12]([C:13]#[C:14][C:15]3[CH:20]=[CH:19][C:18]([NH:21][C:22]([CH:24]4[CH2:29][O:28][CH2:27][CH2:26][N:25]4[C:30](=[O:39])[CH:31]([NH2:38])[C:32]4[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=4)=[O:23])=[CH:17][CH:16]=3)=[CH:11][N:10]([CH3:40])[N:9]=2)[CH:7]=1.[CH:42]1([S:45](Cl)(=[O:47])=[O:46])[CH2:44][CH2:43]1.C(N(CC)CC)C>C(Cl)Cl>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([OH:41])=[C:6]([C:8]2[C:12]([C:13]#[C:14][C:15]3[CH:20]=[CH:19][C:18]([NH:21][C:22]([CH:24]4[CH2:29][O:28][CH2:27][CH2:26][N:25]4[C:30](=[O:39])[CH:31]([NH:38][S:45]([CH:42]4[CH2:44][CH2:43]4)(=[O:47])=[O:46])[C:32]4[CH:33]=[CH:34][CH:35]=[CH:36][CH:37]=4)=[O:23])=[CH:17][CH:16]=3)=[CH:11][N:10]([CH3:40])[N:9]=2)[CH:7]=1

参加物

5

反応物 3

HCID 8471TriethylamineHCID 2760919Cyclopropanesulfonyl chlorideHCID 1363466894-(2-Amino-2-phenyl-acetyl)-morpholine-3-carboxylic acid {4-[3-(5-chloro-2-hydroxy-phenyl)-1-methyl-1H-pyrazol-4-ylethynyl]-phenyl}-amide

生成物 1

HCID 1363466934-(2-Cyclopropanesulfonylamino-2-phenyl-acetyl)-morpholine-3-carboxylic acid {4-[3-(5-chloro-2-hydroxy-phenyl)-1-methyl-1H-pyrazol-4-ylethynyl]-phenyl}-amide収率 60%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

To a solution of compound 9D (4.0 g, 7.02 mmol) in anhydrous CH2Cl2 (100 mL) were added cyclopropanesulfonyl chloride (16D, (1.97 g, 14.03 mmol) and triethylamine (3.91 mL, 28.07 mmol), successively. The reaction mixture was stirred at rt overnight. It was concentrated to small volume and purified with silica column chromatography eluting with dichloromethane/EtOAc to give the title compound (17D) which was recrystallized from hexanes/acetone to provide compound 17D as white powder in ˜60% yield. 1H NMR (CDCl3, 500 MHz) δ 10.66 (s, 1H), 8.67 (s, 1H), 8.18 (s, 1H), 7.67 (d, 2H, J=8.0 Hz), 7.62 (s, 1H), 7.54 (d, 2H, J=8.0 Hz), 7.43 (s, 5H), 7.20 (d, 1H, J=8.5 Hz), 6.97 (d, 1H, J=9.0 Hz), 5.82 (d, 1H, J=8.0 Hz), 5.42 (d, 1H, J=9.0 Hz), 5.20 (s, 1H), 4.67 (d, 1H, J=11.5 Hz), 3.96 (s, 3H), 3.76 (d, 1H, J=11.5 Hz), 3.61 (br s, 2H), 3.44 (dd, 1H, J=12.0, 3.0 Hz), 2.93 (m, 1H), 2.41 (m, 1H), 1.15 (s, 2H), 0.94 (d, 2H, J=5.5 Hz). LCMS (ESI) m/z 696.19 (MNa+), 674.22 (MH+), 351.10 (100). HPLC: tR=4.95 min.

後処理

  1. concentrationIt was concentrated to small volume
  2. custompurified with silica column chromatography
  3. washeluting with dichloromethane/EtOAc

出典と根拠

ORDレコード
ord-5ec27e5eff544530b0b63233a13fd633
出典データセット
uspto-grants-2011_04
特許番号
US07923004B2

反応ノート

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