4-(4-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)cyclohex-3-en-1-yl)morpholine → N-{5-Cyano-6-[4-(morpholin-4-yl)cyclohex-1-en-1-yl]pyridin-3-yl}-5-methyl-1-[5-(trifluoromethyl)pyridin-2-yl]-1H-pyrazole-4-carboxamide

HRID 1748667Notes

Reaction equation

HRID 1748667 reaction equation
Cl[C:2]1[N:7]=[CH:6][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])=[CH:4][C:3]=1[C:27]#[N:28].CC1(C)C(C)(C)OB([C:37]2[CH2:42][CH2:41][CH:40]([N:43]3[CH2:48][CH2:47][O:46][CH2:45][CH2:44]3)[CH2:39][CH:38]=2)O1>O1CCCC1.C(=O)([O-])[O-].[Na+].[Na+].C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:27]([C:3]1[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:24])[F:25])=[CH:19][N:18]=3)[C:15]=2[CH3:16])=[O:10])[CH:6]=[N:7][C:2]=1[C:37]1[CH2:42][CH2:41][CH:40]([N:43]2[CH2:44][CH2:45][O:46][CH2:47][CH2:48]2)[CH2:39][CH:38]=1)#[N:28]

Participants

6

Reactant 2

HCID 592386904-(4-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)cyclohex-3-en-1-yl)morpholineHCID 86692611N-(6-chloro-5-cyanopyridin-3-yl)-5-methyl-1-[5-(trifluoromethyl)pyridin-2-yl]-1H-pyrazole-4-carboxamide

Product 1

HCID 86692612N-{5-Cyano-6-[4-(morpholin-4-yl)cyclohex-1-en-1-yl]pyridin-3-yl}-5-methyl-1-[5-(trifluoromethyl)pyridin-2-yl]-1H-pyrazole-4-carboxamideYield 54.1%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 8028TetrahydrofuranSolventHCID 10340Sodium CarbonateSolvent

Conditions

Temperature
90 °C

Procedure

N-(6-Chloro-5-cyanopyridin-3-yl)-5-methyl-1-[5-(trifluoromethyl)pyridin-2-yl]-1H-pyrazole-4-carboxamide (200 mg), 4-[4-(4,4,5,5-tetramethyl-[1,3,2] dioxaborolan-2-yl)cyclohex-3-en-1-yl]morpholine (159 mg) described in Reference Example 166 and tetrakis(triphenylphosphine)palladium (57 mg) were dissolved in a mixture of tetrahydrofuran (1 ml) and 1M aqueous solution of sodium carbonate (0.54 ml), and stirred at 90° C. After completion of the reaction, the reaction solution was left stand, filtered through Celite, washed with chloroform and the filtrate was concentrated. Water was added to the resulting residue and the precipitate was filtered. The obtained solid was refluxed in ethanol, the resulting solution was left stand, the precipitated solid was collected by filtration and dried in vacuo to give the titled compound (143 mg) as a pale yellow solid.

Workup

  1. customAfter completion of the reaction
  2. waitthe reaction solution was left stand
  3. filtrationfiltered through Celite
  4. washwashed with chloroform
  5. concentrationthe filtrate was concentrated
  6. additionWater was added to the resulting residue
  7. filtrationthe precipitate was filtered
  8. temperatureThe obtained solid was refluxed in ethanol
  9. waitthe resulting solution was left stand
  10. filtrationthe precipitated solid was collected by filtration
  11. customdried in vacuo

Sources & evidence

ORD record
ord-b4bd4ea783a74cb895ac0723fb536f4f
Source dataset
uspto-grants-2015_10
Patent number
US09150555B2

Reaction notes

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