Methanesulfonic Acid → HCID 86641693, compound

HRID 2060733Notes

Reaction equation

HRID 2060733 reaction equation
[CH3:1][N:2]1[CH:6]=[C:5]([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:27]([NH:29][C:30]5[CH:35]=[CH:34][C:33]([F:36])=[CH:32][CH:31]=5)=[O:28])[CH2:26][CH2:25]4)=[O:23])=[C:16]([F:37])[CH:15]=3)[CH:10]=[CH:9][N:8]=2)[C:4]([CH3:38])=[N:3]1.[CH3:39][S:40]([OH:43])(=[O:42])=[O:41]>C1COCC1>[S:40]([OH:43])(=[O:42])(=[O:41])[CH3:39].[CH3:1][N:2]1[CH:6]=[C:5]([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:27]([NH:29][C:30]5[CH:31]=[CH:32][C:33]([F:36])=[CH:34][CH:35]=5)=[O:28])[CH2:26][CH2:25]4)=[O:23])=[C:16]([F:37])[CH:15]=3)[CH:10]=[CH:9][N:8]=2)[C:4]([CH3:38])=[N:3]1

Participants

4

Reactant 2

HCID 6395Methanesulfonic AcidHCID 67398712HCID 67398712, compound

Product 1

HCID 86641693HCID 86641693, compoundYield 71.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

N-(4-(2-(1,3-Dimethyl-1H-pyrazol-4-yl)pyridin-4-yloxy)-2,5-difluorophenyl)-N′-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide (0.278 g, 0.533 mmol) was dissolved in THF (5 ml) and warmed until reflux. Methanesulfonic acid (0.035 ml, 0.533 mmol) was added. A precipitate immediately formed. The mixture was sonicated for 10 min and allowed to cool to RT. The precipitate was filtered off and dried overnight in the drying pistol (80° C.) to yield N-(4-(2-(1,3-Dimethyl-1H-pyrazol-4-yl)pyridin-4-yloxy)-2,5-difluorophenyl)-N′-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide mesylate (234 mg, 71.1% yie3ld). 1H NMR (400 MHz, DMSO-d6): δ 11.20 (s, 1H), 9.71 (s, 1H), 8.57 (d, 1H), 8.19-8.14 (m, 1H), 7.90 (s, 1H), 7.66-7.62 (m, 1H), 7.58-7.55 (m, 2H), 7.38 (s, 1H), 7.19-7.14 (m, 2H), 7.05-7.02 (m, 1H), 3.79 (s, 3H), 2.34 (s, 3H), 2.29 (s, 3H), 1.68-1.65 (m, 2H), 1.58-1.56 (m, 2H); MS (ESI) m/z: 522.2 (M+H+).

Workup

  1. temperaturewarmed
  2. temperatureuntil reflux
  3. customA precipitate immediately formed
  4. customThe mixture was sonicated for 10 min
  5. filtrationThe precipitate was filtered off
  6. customdried overnight in the drying pistol (80° C.)

Sources & evidence

ORD record
ord-4d48243833434956825a22987eae3819
Source dataset
uspto-grants-2012_10
Patent number
US08278331B2

Reaction notes

Loading…