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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
ノート
印刷プレビュー

反応式

HRID 424135 の反応式
[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]
参加物実験手順後処理出典と根拠反応ノート

参加物

5

反応物 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

生成物 1

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

試薬・触媒・溶媒 1

HCID 8028
Tetrahydrofuran
溶媒

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-c508c5df546d4a82b9d20327f34244ef
出典データセット
uspto-grants-2012_01
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08101773B2

反応ノート

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