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 2075777노트

반응식

HRID 2075777 반응식
[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

참가 물질

5

반응물 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

생성물 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}-amide수율 49%

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

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.

후처리

  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)

출처 및 근거

ORD 기록
ord-94627a2a609945998a90d1ef59051c2c
출처 데이터셋
uspto-grants-2011_04
특허 번호
US07923004B2

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