Hydrochloric Acid → N-(2,5-difluoro-4-((2-(1-(2-hydroxyethyl)-1H-pyrazol-4-yl)pyridin-4-yl)oxy)phenyl)-1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxamide hydrochloride

HRID 1472618Notes

Reaction equation

HRID 1472618 reaction equation
[Si]([O:8][CH2:9][CH2:10][N:11]1[CH:15]=[C:14]([C:16]2[CH:21]=[C:20]([O:22][C:23]3[C:28]([F:29])=[CH:27][C:26]([NH:30][C:31]([C:33]4[C:34](=[O:46])[N:35]([C:39]5[CH:44]=[CH:43][C:42]([F:45])=[CH:41][CH:40]=5)[CH:36]=[CH:37][CH:38]=4)=[O:32])=[C:25]([F:47])[CH:24]=3)[CH:19]=[CH:18][N:17]=2)[CH:13]=[N:12]1)(C(C)(C)C)(C)C.CO.[ClH:50]>>[ClH:50].[F:47][C:25]1[CH:24]=[C:23]([O:22][C:20]2[CH:19]=[CH:18][N:17]=[C:16]([C:14]3[CH:13]=[N:12][N:11]([CH2:10][CH2:9][OH:8])[CH:15]=3)[CH:21]=2)[C:28]([F:29])=[CH:27][C:26]=1[NH:30][C:31]([C:33]1[C:34](=[O:46])[N:35]([C:39]2[CH:40]=[CH:41][C:42]([F:45])=[CH:43][CH:44]=2)[CH:36]=[CH:37][CH:38]=1)=[O:32]

Participants

4

Reactant 3

HCID 313Hydrochloric AcidHCID 887MethanolHCID 90426859N-(4-((2-(1-(2-((tert-butyldimethylsilyl)oxy)ethyl)-1H-pyrazol-4-yl)pyridin-4-yl)oxy)-2,5-difluorophenyl)-1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxamide

Product 1

HCID 90426903N-(2,5-difluoro-4-((2-(1-(2-hydroxyethyl)-1H-pyrazol-4-yl)pyridin-4-yl)oxy)phenyl)-1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxamide hydrochlorideYield 89%

Procedure

A solution of N-(4-((2-(1-(2-((tert-butyldimethylsilyl)oxy)ethyl)-1H-pyrazol-4-yl)pyridin-4-yl)oxy)-2,5-difluorophenyl)-1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxamide (0.121 g, 0.183 mmol) in 1.0M HCl in MeOH (2.75 mL, 2.75 mmol) was stirred at RT for 1 h. The solids were collected via filtration, rinsed with a small amount of MeOH and dried under high vacuum at 80° C. to afford N-(2,5-difluoro-4-((2-(1-(2-hydroxyethyl)-1H-pyrazol-4-yl)pyridin-4-yl)oxy)phenyl)-1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxamide hydrochloride (95 mg, 89%) as a white solid. 1H NMR (400 MHz, DMSO-d6): δ 12.45 (s, 1H); 8.54-8.58 (m, 4H); 8.30 (s, 1H); 8.12 (dd, J=6.6, 2.2 Hz, 1H); 7.63-7.72 (m, 2H); 7.54-7.56 (m, 2H); 7.37 (m, 2H); 7.13 (s, 1H); 6.71 (m, 1H); 4.15 (t, J=5.3 Hz, 2H); 3.70 (t, J=5.4 Hz, 2H); MS (ESI) m/z: 548.2 (M+H+).

Workup

  1. filtrationThe solids were collected via filtration
  2. washrinsed with a small amount of MeOH
  3. customdried under high vacuum at 80° C.

Sources & evidence

ORD record
ord-34fd44f145cf43bd8fc1093f89e85152
Source dataset
uspto-grants-2015_04
Patent number
US09012635B2

Reaction notes

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