Dimethylformamide → 5-Methyl-N-{5-[4-(morpholin-4-yl)cyclohex-1-en-1-yl]pyrazin-2-yl}-1-[5-(trifluoromethyl)-pyridin-2-yl]-1H-pyrazole-4-carboxamide

HRID 1748665Notes

Reaction equation

HRID 1748665 reaction equation
Br[C:2]1[N:3]=[CH:4][C:5]([NH:8][C:9]([C:11]2[CH:12]=[N:13][N:14]([C:17]3[CH:22]=[CH:21][C:20]([C:23]([F:26])([F:25])[F:24])=[CH:19][N:18]=3)[C:15]=2[CH3:16])=[O:10])=[N:6][CH:7]=1.CC1(C)C(C)(C)OB([C:35]2[CH2:40][CH2:39][CH:38]([N:41]3[CH2:46][CH2:45][O:44][CH2:43][CH2:42]3)[CH2:37][CH:36]=2)O1.C(=O)([O-])[O-].[Na+].[Na+].CN(C)C=O>O1CCOCC1.C1(C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)[Pd][P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.O>[CH3:16][C:15]1[N:14]([C:17]2[CH:22]=[CH:21][C:20]([C:23]([F:26])([F:25])[F:24])=[CH:19][N:18]=2)[N:13]=[CH:12][C:11]=1[C:9]([NH:8][C:5]1[CH:4]=[N:3][C:2]([C:35]2[CH2:40][CH2:39][CH:38]([N:41]3[CH2:42][CH2:43][O:44][CH2:45][CH2:46]3)[CH2:37][CH:36]=2)=[CH:7][N:6]=1)=[O:10]

Participants

8

Reactant 4

HCID 6228DimethylformamideHCID 10340Sodium CarbonateHCID 592386904-(4-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)cyclohex-3-en-1-yl)morpholineHCID 86692610N-(5-bromopyrazin-2-yl)-5-methyl-1-[5-(trifluoromethyl)pyridin-2-yl]-1H-pyrazole-4-carboxamide

Product 1

HCID 866926095-Methyl-N-{5-[4-(morpholin-4-yl)cyclohex-1-en-1-yl]pyrazin-2-yl}-1-[5-(trifluoromethyl)-pyridin-2-yl]-1H-pyrazole-4-carboxamideYield 44.1%

Reagents, catalysts & solvents 3

HCID 178419050HCID 178419050, compoundCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of N-(5-bromopyrazin-2-yl)-5-methyl-1-[5-(trifluoromethyl)pyridin-2-yl]-1H-pyrazole-4-carboxamide (300 mg), 4-[4-(4,4,5,5-tetramethyl[1,3,2] dioxaborolan-2-yl)cyclohex-3-en-1-yl]morpholin (185 mg), tetrakis(trophenylphosphine)palladium (0) (81 mg) and sodium carbonate (186 mg) in 1,4-dioxane (7.0 ml) was stirred at 90° C. for four hours. Then, N,N-dimethylformamide (7.0 ml) and bis(diphenylphosphine)ferrocenepalladium (II) dichloride dichloromethane adduct (57 mg) were added at room temperature and stirred at 90° C. for five hours. After completion of the reaction, the reaction solution was cooled to room temperature, water was added, and the precipitated solid was collected by filtration. The resulting residue was purified with silica gel column chromatography (chloroform/methanol) twice to give the titled compound (143 mg) as a white solid.

Workup

  1. stirringstirred at 90° C. for five hours
  2. customAfter completion of the reaction
  3. temperaturethe reaction solution was cooled to room temperature
  4. filtrationthe precipitated solid was collected by filtration
  5. customThe resulting residue was purified with silica gel column chromatography (chloroform/methanol) twice

Sources & evidence

ORD record
ord-a7ac70f53baf4ac9a4506db65c9e35ed
Source dataset
uspto-grants-2015_10
Patent number
US09150555B2

Reaction notes

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