Diethyl Ether → N-(4-((2-(cyclopropanecarboxamido)pyridin-4-yl)oxy)-2,5-difluorophenyl)-4-ethoxy-1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxamide methanesulfonate

HRID 1050864Notes

Reaction equation

HRID 1050864 reaction equation
[CH:1]1([C:4]([NH:6][C:7]2[CH:12]=[C:11]([O:13][C:14]3[C:19]([F:20])=[CH:18][C:17]([NH:21][C:22]([C:24]4[C:25](=[O:40])[N:26]([C:33]5[CH:38]=[CH:37][C:36]([F:39])=[CH:35][CH:34]=5)[CH:27]=[CH:28][C:29]=4[O:30][CH2:31][CH3:32])=[O:23])=[C:16]([F:41])[CH:15]=3)[CH:10]=[CH:9][N:8]=2)=[O:5])[CH2:3][CH2:2]1.[CH3:42][S:43]([OH:46])(=[O:45])=[O:44].CCOCC>CC#N>[CH3:42][S:43]([OH:46])(=[O:45])=[O:44].[CH:1]1([C:4]([NH:6][C:7]2[CH:12]=[C:11]([O:13][C:14]3[C:19]([F:20])=[CH:18][C:17]([NH:21][C:22]([C:24]4[C:25](=[O:40])[N:26]([C:33]5[CH:34]=[CH:35][C:36]([F:39])=[CH:37][CH:38]=5)[CH:27]=[CH:28][C:29]=4[O:30][CH2:31][CH3:32])=[O:23])=[C:16]([F:41])[CH:15]=3)[CH:10]=[CH:9][N:8]=2)=[O:5])[CH2:3][CH2:2]1

Participants

5

Reactant 3

HCID 3283Diethyl EtherHCID 6395Methanesulfonic AcidHCID 71575771N-(4-((2-(cyclopropanecarboxamido)pyridin-4-yl)oxy)-2,5-difluorophenyl)-4-ethoxy-1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxamide

Product 1

HCID 86703362N-(4-((2-(cyclopropanecarboxamido)pyridin-4-yl)oxy)-2,5-difluorophenyl)-4-ethoxy-1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxamide methanesulfonateYield 44.5%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
80 °C

Procedure

A suspension of N-(4-((2-(cyclopropanecarboxamido)pyridin-4-yl)oxy)-2,5-difluorophenyl)-4-ethoxy-1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxamide (0.029 g, 0.051 mmol) in MeCN (0.5 mL) was heated to 80° C., treated with methanesulfonic acid (3.34 μl, 0.051 mmol), then cooled to RT and stirred overnight. Ether was added drop wise until solids precipitated. The mixture was stirred for several hours. The solids were collected by filtration, rinsed with ether and dried under vacuum to afford N-(4-((2-(cyclopropanecarboxamido)pyridin-4-yl)oxy)-2,5-difluorophenyl)-4-ethoxy-1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxamide methanesulfonate (15 mg, 44% yield) as a white solid. 1H NMR (400 MHz, DMSO-d6): δ 11.22 (s, 1 H), 10.99 (s, 1 H), 8.33 (dd, J=12.6, 7.2 Hz, 1 H), 8.20 (d, J=5.8 Hz, 1 H), 7.92 (d, J=7.8 Hz, 1 H), 7.63-7.45 (m, 4 H), 7.36 (m, 2 H), 6.79 (d, J=5.7 Hz, 1 H), 6.55 (d, J=7.9 Hz, 1 H), 4.28 (q, J=7.0 Hz, 2 H), 2.29 (s, 3 H), 1.93 (m, 1 H), 1.33 (t, J=7.0 Hz, 3 H), 0.77 (m, 4 H); MS (ESI) m/z: 565.2 (M+H+).

Workup

  1. temperaturecooled to RT
  2. customprecipitated
  3. stirringThe mixture was stirred for several hours
  4. filtrationThe solids were collected by filtration
  5. washrinsed with ether
  6. customdried under vacuum

Sources & evidence

ORD record
ord-44b3200e864e422f97efcf0cbcdd7b08
Source dataset
uspto-grants-2016_07
Patent number
US09387202B2

Reaction notes

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