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 424135Notes

Reaction equation

HRID 424135 reaction equation
[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]

Participants

5

Reactant 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

Product 1

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

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

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).

Workup

  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

Sources & evidence

ORD record
ord-c508c5df546d4a82b9d20327f34244ef
Source dataset
uspto-grants-2012_01
Patent number
US08101773B2

Reaction notes

Loading…