Methanesulfonic Acid → HCID 86641694, compound

HRID 2060734Notes

Reaction equation

HRID 2060734 reaction equation
[S:1]([OH:5])(=[O:4])(=[O:3])[CH3:2].C[N:7]1[CH:11]=[C:10]([C:12]2[CH:17]=[C:16]([O:18][C:19]3[C:24]([F:25])=[CH:23][C:22]([NH:26][C:27]([C:29]4([C:32]([NH:34][C:35]5[CH:40]=[CH:39][C:38]([F:41])=[CH:37][CH:36]=5)=[O:33])[CH2:31][CH2:30]4)=[O:28])=[C:21]([F:42])[CH:20]=3)[CH:15]=[CH:14][N:13]=2)[C:9]([CH3:43])=[N:8]1.[CH3:44]S(O)(=O)=O>C1COCC1.CCOCC>[S:1]([OH:5])(=[O:4])(=[O:3])[CH3:2].[CH3:44][N:8]1[C:9]([CH3:43])=[C:10]([C:12]2[CH:17]=[C:16]([O:18][C:19]3[C:24]([F:25])=[CH:23][C:22]([NH:26][C:27]([C:29]4([C:32]([NH:34][C:35]5[CH:40]=[CH:39][C:38]([F:41])=[CH:37][CH:36]=5)=[O:33])[CH2:30][CH2:31]4)=[O:28])=[C:21]([F:42])[CH:20]=3)[CH:15]=[CH:14][N:13]=2)[CH:11]=[N:7]1

Participants

5

Reactant 2

HCID 6395Methanesulfonic AcidHCID 86641693HCID 86641693, compound

Product 1

HCID 86641694HCID 86641694, compoundYield 82.5%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent

Procedure

N-(4-(2-(1,5-Dimethyl-1H-pyrazol-4-yl)pyridin-4-yloxy)-2,5-difluorophenyl)-N′-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide from Example 49 (0.081 g, 0.155 mmol) was dissolved in THF (2.5 ml) and warmed until reflux. Methanesulfonic acid (10.09 μl, 0.155 mmol) was added and the mixture cooled to RT. The mixture was slowly diluted with Et2O (5 ml). A precipitate immediately began to form upon addition. After the addition was complete, the mixture was sonicated for 20 min. The precipitate was filtered off to yield N-(4-(2-(1,5-dimethyl-1H-pyrazol-4-yl)pyridin-4-yloxy)-2,5-difluorophenyl)-N′-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide mesylate (79 mg, 82% yield). 1H NMR (400 MHz, DMSO-d6): δ 11.18 (s, 1H), 9.72 (s, 1H), 8.52 (d, 1H), 8.20-8.14 (m, 2H), 7.63-7.56 (m, 3H), 7.25 (s, 1H), 7.18-7.14 (m, 2H), 6.99-6.94 (m, 1H), 3.74 (s, 3H), 2.35 (s, 3H), 2.28 (s, 3H), 1.67-1.64 (m, 2H), 1.58-1.55 (m, 2H); MS (ESI) m/z: 522.2 (M+H+).

Workup

  1. temperaturewarmed
  2. temperatureuntil reflux
  3. customto form upon addition
  4. additionAfter the addition
  5. customthe mixture was sonicated for 20 min
  6. filtrationThe precipitate was filtered off

Sources & evidence

ORD record
ord-324a81bb66364cf4bbb385382cf8a0c8
Source dataset
uspto-grants-2012_10
Patent number
US08278331B2

Reaction notes

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