Cesium carbonate → 5-Methyl-N-{5-methyl-6-[4-(3-oxomorpholin-4-yl)cyclohex-1-en-1-yl]pyridin-3-yl}-1-[5-(trifluoromethyl)pyridin-2-yl]-1H-pyrazole-4-carboxamide

HRID 1748635Notes

Reaction equation

HRID 1748635 reaction equation
Br[C:2]1[CH:3]=[C:4]([CH3:21])[C:5]([C:8]2[CH2:13][CH2:12][CH:11]([N:14]3[CH2:19][CH2:18][O:17][CH2:16][C:15]3=[O:20])[CH2:10][CH:9]=2)=[N:6][CH:7]=1.[CH3:22][C:23]1[N:27]([C:28]2[CH:33]=[CH:32][C:31]([C:34]([F:37])([F:36])[F:35])=[CH:30][N:29]=2)[N:26]=[CH:25][C:24]=1[C:38]([NH2:40])=[O:39].C(=O)([O-])[O-].[Cs+].[Cs+].[Cl-].[NH4+]>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.O1CCOCC1>[CH3:22][C:23]1[N:27]([C:28]2[CH:33]=[CH:32][C:31]([C:34]([F:36])([F:37])[F:35])=[CH:30][N:29]=2)[N:26]=[CH:25][C:24]=1[C:38]([NH:40][C:2]1[CH:7]=[N:6][C:5]([C:8]2[CH2:13][CH2:12][CH:11]([N:14]3[CH2:19][CH2:18][O:17][CH2:16][C:15]3=[O:20])[CH2:10][CH:9]=2)=[C:4]([CH3:21])[CH:3]=1)=[O:39]

Participants

8

Reactant 4

HCID 10796Cesium carbonateHCID 25517Ammonium ChlorideHCID 471413721-(5-trifluoromethylpyridin-2-yl)-5-methyl-1H-pyrazole-4-carboxamideHCID 866925624-[4-(5-Bromo-3-methylpyridin-2-yl)cyclohex-3-en-1-yl]morpholin-3-one

Product 1

HCID 866925725-Methyl-N-{5-methyl-6-[4-(3-oxomorpholin-4-yl)cyclohex-1-en-1-yl]pyridin-3-yl}-1-[5-(trifluoromethyl)pyridin-2-yl]-1H-pyrazole-4-carboxamideYield 73.5%

Reagents, catalysts & solvents 3

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

Conditions

Temperature
110 °C

Procedure

1,4-Dioxane (2 ml) was added to 4-[4-(5-bromo-3-methylpyridin-2-yl)cyclohex-3-en-1-yl]morpholin-3-one (150 mg) described in Reference Example 187, 5-methyl-1-[5-(trifluoromethyl)pyridin-2-yl]-1H-pyrazole-4-carboxamide (115 mg) described in Reference Example 120, palladium (II) acetate (3.8 mg), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (14.8 mg) and cesium carbonate (195 mg) and stirred at 110° C. for five hours. After the reaction, the reaction solution was cooled to room temperature, a saturated aqueous solution of ammonium chloride was added and the precipitated solid was filtered. The resulted solid was purified with a silica gel column chromatography (chloroform/methanol), suspended and washed with ethanol to give the titled compound (169 mg) as a white solid.

Workup

  1. customAfter the reaction
  2. temperaturethe reaction solution was cooled to room temperature
  3. filtrationthe precipitated solid was filtered
  4. customThe resulted solid was purified with a silica gel column chromatography (chloroform/methanol)
  5. washwashed with ethanol

Sources & evidence

ORD record
ord-d979495ce2704e3491553de9329c7288
Source dataset
uspto-grants-2015_10
Patent number
US09150555B2

Reaction notes

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