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Triethylamine → ethyl 3-(3-tert-butyl-5-{[(2-fluoro-4-{[2-(methylcarbamoyl)-pyridin-4-yl]oxy}phenyl)carbamoyl]amino}-1H-pyrazol-1-yl)benzoate

HRID 424135
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HRID 424135 반응식
[C:1]([C:5]1[CH:9]=[C:8]([NH:10][C:11](OC2C=CC=CC=2)=[O:12])[N:7]([C:20]2[CH:21]=[C:22]([CH:28]=[CH:29][CH:30]=2)[C:23]([O:25][CH2:26][CH3:27])=[O:24])[N:6]=1)([CH3:4])([CH3:3])[CH3:2].[NH2:31][C:32]1[CH:48]=[CH:47][C:35]([O:36][C:37]2[CH:42]=[CH:41][N:40]=[C:39]([C:43]([NH:45][CH3:46])=[O:44])[CH:38]=2)=[CH:34][C:33]=1[F:49].C(N(CC)CC)C>C1COCC1>[C:1]([C:5]1[CH:9]=[C:8]([NH:10][C:11](=[O:12])[NH:31][C:32]2[CH:48]=[CH:47][C:35]([O:36][C:37]3[CH:42]=[CH:41][N:40]=[C:39]([C:43](=[O:44])[NH:45][CH3:46])[CH:38]=3)=[CH:34][C:33]=2[F:49])[N:7]([C:20]2[CH:21]=[C:22]([CH:28]=[CH:29][CH:30]=2)[C:23]([O:25][CH2:26][CH3:27])=[O:24])[N:6]=1)([CH3:3])([CH3:2])[CH3:4]
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참가 물질

5

반응물 3

HCID 8471TriethylamineHCID 468352194-(4-Amino-3-fluorophenoxy)-N-methylpyridine-2-carboxamideHCID 59234717ethyl 3-{3-tert-butyl-5-[(phenoxycarbonyl)amino]-1H-pyrazol-1-yl}benzoate

생성물 1

HCID 59234716ethyl 3-(3-tert-butyl-5-{[(2-fluoro-4-{[2-(methylcarbamoyl)-pyridin-4-yl]oxy}phenyl)carbamoyl]amino}-1H-pyrazol-1-yl)benzoate수율 57.6%

시약·촉매·용매 1

HCID 8028
Tetrahydrofuran
용매

실험 절차

A solution of ethyl 3-{3-tert-butyl-5-[(phenoxycarbonyl)amino]-1H-pyrazol-1-yl}benzoate (9.36 g, 22.0 mmol), 4-(4-amino-3-fluorophenoxy)-N-methylpyridine-2-carboxamide (5.0 g, 19.1 mmol; prepared as described in Dumas et al., PCT Int. Appl. WO 2004078748 (2004)) and triethyl amine (3.87 g, 38.3 mmol) in anhydrous THF (100 mL) was stirred at room temperature overnight. The crude product was purified by column chromatography (CH2Cl2 plus 1% to 3% of 2M NH3 in MeOH), followed by recrystallization from EtOAc/hexanes to give the desired product as an off-white crystalline solid (6.32 g, 57%). MS m/z 575.1 (M+H)+; calcd. mass 574. Retention time (LC-MS): 3.75 min. 1H-NMR (DMSO-d6): δ 8.97 (m, 1H); 8.89 (m, 1H); 8.80 (m, 1H); 8.52 (d, J=5.6 Hz, 1H); 8.16 (t, 1H); 8.06 (m, 1H); 7.99 (m, 1H); 7.85 (m, 1H); 7.71 (t, 1H); 7.39 (m, 1H); 7.33 (m, 1H); 7.17 (m, 1H); 7.06 (m, 1H); 6.42 (s, 1H); 4.36 (q, 2H); 2.78 (d, J=5.2 Hz, 3H); 1.31 (m, 12H).

후처리

  1. customThe crude product was purified by column chromatography (CH2Cl2 plus 1% to 3% of 2M NH3 in MeOH)
  2. customfollowed by recrystallization from EtOAc/hexanes

출처 및 근거

ORD 기록
ord-c508c5df546d4a82b9d20327f34244ef
출처 데이터셋
uspto-grants-2012_01
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08101773B2

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