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

HRID 2075777ノート

反応式

HRID 2075777 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([C:45](O)=[O:46])[CH2:44][CH2:43]1.CC(C)N=C=NC(C)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][C:45]([CH:42]4[CH2:44][CH2:43]4)=[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 12734DiisopropylcarbodiimideHCID 15655Cyclopropanecarboxylic acidHCID 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 1363466904-[2-(Cyclopropanecarbonyl-amino)-2-phenyl-acetyl]-morpholine-3-carboxylic acid {4-[3-(5-chloro-2-hydroxy-phenyl)-1-methyl-1H-pyrazol-4-ylethynyl]-phenyl}-amide収率 49%

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) and cyclopropanecarboxylic acid (10D, (0.91 g, 10.53 mmol) in anhydrous CH2Cl2 (100 mL) was added DIPC (1.63 mL, 10.53 mmol). The reaction mixture was stirred at rt overnight. It was filtered to remove diisopropylurea. The filtrate was purified with silica column chromatography eluting with dichloromethane/EtOAc (v/v 1/1, 7/1, 4/1) to give the title compound (11D, 3.4 g, crude), which was recrystallized from hexanes/acetone to provide pure compound 11D (2.2 g) as white powder in 49% yield. 1H NMR (CDCl3, 500 MHz) δ 10.68 (s, 1H), 8.75 (s, 1H), 8.71 (s, 1H), 7.90 (d, 2H, J=8.5 Hz), 7.63 (s, 1H), 7.56 (d, 2H, J=9.0 Hz), 7.50 (m, 2H), 7.45 (m, 3H), 7.20 (dd, 1H, J=8.5, 2.5 Hz), 6.97 (d, 1H, J=9.0 Hz), 6.57 (s, 1H), 5.69 (d, 1H, J=5.5 Hz), 5.23 (s, 1H), 4.82 (d, 1H, J=12.0 Hz), 3.97 (s, 3H), 3.81 (d, 1H, J=11.5 Hz), 3.72 (d, 1H, J=12.5 Hz), 3.64 (t, 1H, J=12.0 Hz), 3.43 (dd, 1H, J=11.0, 3.0 Hz), 3.11 (t, 1H, J=11.5 Hz), 1.49 (m, 1H), 1.00 (m, 2H), 0.84 (m, 2H). LCMS (ESI) m/z 669.43 (MNa+), 638.39 (MH+), 437.28. HPLC: tR=4.98 min.

後処理

  1. filtrationIt was filtered
  2. customto remove diisopropylurea
  3. customThe filtrate was purified with silica column chromatography
  4. washeluting with dichloromethane/EtOAc (v/v 1/1, 7/1, 4/1)

出典と根拠

ORDレコード
ord-94627a2a609945998a90d1ef59051c2c
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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