Methanesulfonic Acid → 5-Methyl-N-{5-methyl-6-[4-(morpholin-4-yl)cyclohex-1-en-1-yl]pyridin-3-yl}-1-[5-(trifluoromethyl)pyridin-2-yl]-1H-pyrazole-4-carboxamide mesylate

HRID 1748624Notes

Reaction equation

HRID 1748624 reaction equation
[F:1][C:2]([F:19])([F:18])[C:3]1[CH:4]=[CH:5][C:6]([N:9]2[C:13]([CH3:14])=[C:12]([C:15]([NH2:17])=[O:16])[CH:11]=[N:10]2)=[N:7][CH:8]=1.[N:20]1([CH:26]2[CH2:31][CH2:30][C:29]([C:32]3[C:37]([CH3:38])=[CH:36][C:35](Br)=[CH:34][N:33]=3)=[CH:28][CH2:27]2)[CH2:25][CH2:24][O:23][CH2:22][CH2:21]1.C(=O)([O-])[O-].[Cs+].[Cs+].[CH3:46][S:47]([OH:50])(=[O:49])=[O:48]>O1CCOCC1.C(Cl)(Cl)Cl.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1(P(C2C=CC=CC=2)C2C3OC4C(=CC=CC=4P(C4C=CC=CC=4)C4C=CC=CC=4)C(C)(C)C=3C=CC=2)C=CC=CC=1>[S:47]([OH:50])(=[O:49])(=[O:48])[CH3:46].[CH3:14][C:13]1[N:9]([C:6]2[CH:5]=[CH:4][C:3]([C:2]([F:1])([F:18])[F:19])=[CH:8][N:7]=2)[N:10]=[CH:11][C:12]=1[C:15]([NH:17][C:35]1[CH:34]=[N:33][C:32]([C:29]2[CH2:30][CH2:31][CH:26]([N:20]3[CH2:21][CH2:22][O:23][CH2:24][CH2:25]3)[CH2:27][CH:28]=2)=[C:37]([CH3:38])[CH:36]=1)=[O:16]

Participants

9

Reactant 4

HCID 6395Methanesulfonic AcidHCID 10796Cesium carbonateHCID 471413721-(5-trifluoromethylpyridin-2-yl)-5-methyl-1H-pyrazole-4-carboxamideHCID 866924794-[4-(5-Bromo-3-methylpyridin-2-yl)cyclohex-3-en-1-yl]morpholine

Product 1

HCID 866925665-Methyl-N-{5-methyl-6-[4-(morpholin-4-yl)cyclohex-1-en-1-yl]pyridin-3-yl}-1-[5-(trifluoromethyl)pyridin-2-yl]-1H-pyrazole-4-carboxamide mesylate

Reagents, catalysts & solvents 4

HCID 167845palladium(II) acetateCatalystHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)CatalystHCID 6212ChloroformSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A suspension of 1-(5-trifluoromethylpyridin-2-yl)-5-methyl-1H-pyrazole-4-carboxamide (2.2 g) described in Reference Example 120, 2-(4-(morpholin-4-yl)cyclohex-1-en-1-yl)-3-methyl-5-bromopyridine (2.75 g) described in Reference Example 107, 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (152 mg), palladium acetate (39 mg) and cesium carbonate (4.01 g) in 1,4-dioxane (30 ml) was stirred at 100° C. After the reaction, the reaction solution was left stand, ice water was added and extracted with chloroform. The organic layer was dried over anhydrous sodium sulfate, and concentrated. The resulting residue was purified with a silica gel column chromatography (chloroform/methanol), washed with ethanol and the resulting solid was filtered and dried at 60° C. in vacuo to give a white solid. Methanesulfonic acid (0.326 ml) was added to a solution of the resulting solid in chloroform (200 ml) and stirred at room temperature for three hours. Then, the solvent was evaporated, ethanol was added and the precipitated solid was filtered and dried at 60° C. in vacuo to give the titled compound (2.9 g) as a white solid.

Workup

  1. customAfter the reaction
  2. additionwas added
  3. extractionextracted with chloroform
  4. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  5. concentrationconcentrated
  6. customThe resulting residue was purified with a silica gel column chromatography (chloroform/methanol)
  7. washwashed with ethanol
  8. filtrationthe resulting solid was filtered
  9. customdried at 60° C. in vacuo
  10. customto give a white solid
  11. stirringstirred at room temperature for three hours
  12. customThen, the solvent was evaporated
  13. additionethanol was added
  14. filtrationthe precipitated solid was filtered
  15. customdried at 60° C. in vacuo

Sources & evidence

ORD record
ord-432cc8a7aeb34fa7a66a54e5136bf816
Source dataset
uspto-grants-2015_10
Patent number
US09150555B2

Reaction notes

Loading…