Methanesulfonic Acid → HCID 86641693, compound

HRID 450483Notes

Reaction equation

HRID 450483 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% yield). 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-0d8214a53de649cd8ac8e6dbd51b1ab8
Source dataset
uspto-grants-2013_07
Patent number
US08486951B2

Reaction notes

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