Cesium carbonate → 6-Trifluoromethyl-pyridine-2-carboxylic acid[6-(4-tert-butylcarbamoyl-piperidin-1-ylmethyl)-pyrimidin-4-yl]-amide

HRID 1486749Notes

Reaction equation

HRID 1486749 reaction equation
[C:1]([NH:5][C:6]([CH:8]1[CH2:13][CH2:12][N:11]([CH2:14][B-](F)(F)F)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].Cl[C:20]1[N:25]=[CH:24][N:23]=[C:22]([NH:26][C:27]([C:29]2[CH:34]=[CH:33][CH:32]=[C:31]([C:35]([F:38])([F:37])[F:36])[N:30]=2)=[O:28])[CH:21]=1.CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.C([O-])([O-])=O.[Cs+].[Cs+]>C1COCC1.O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[C:1]([NH:5][C:6]([CH:8]1[CH2:13][CH2:12][N:11]([CH2:14][C:20]2[N:25]=[CH:24][N:23]=[C:22]([NH:26][C:27]([C:29]3[CH:34]=[CH:33][CH:32]=[C:31]([C:35]([F:36])([F:38])[F:37])[N:30]=3)=[O:28])[CH:21]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenyl2×HCID 867065656-Trifluoromethyl-pyridine-2-carboxylic acid (6-chloro-pyrimidin-4-yl)-amideHCID 131736817((4-(Tert-butylcarbamoyl)piperidin-1-yl)methyl)trifluoroborate

Product 1

HCID 1185219266-Trifluoromethyl-pyridine-2-carboxylic acid[6-(4-tert-butylcarbamoyl-piperidin-1-ylmethyl)-pyrimidin-4-yl]-amide

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 21881883Oxolane--water (1/1)Solvent

Conditions

Temperature
80 °C

Procedure

To a solution of ((4-(tert-butylcarbamoyl)piperidin-1-yl)methyl)trifluoroborate (45 mg, 0.169 mmol) in THF/water 4:1 (3 mL) are added 6-trifluoromethyl-pyridine-2-carboxylic acid (6-chloro-pyrimidin-4-yl)-amide (51.2 mg, 0.169 mmol), palladium (II) acetate, (0.949 mg, 0.00423 mmol,), X-Phos, (2-dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl) (4.84 mg, 0.0101 mmol) and Cs2CO3, (165 mg, 0.507 mmol). The mixture is purged with argon and is stirred overnight in a sealed tube at 80° C. The mixture is let to cool down. Water (3 mL) and AcOEt (5 mL) are added and the aqueous phase is extracted with AcOEt (10 mL). The organic phase is dried over MgSO4, filtered and evaporated. The residue is purified by prep HPLC E delivering the title compound (27 mg, 30%) as a white powder, LC-MS A: tR=0.74 min; [M+H]+=465.4.

Workup

  1. customThe mixture is purged with argon
  2. temperatureto cool down
  3. additionWater (3 mL) and AcOEt (5 mL) are added
  4. extractionthe aqueous phase is extracted with AcOEt (10 mL)
  5. dry with materialThe organic phase is dried over MgSO4
  6. filtrationfiltered
  7. customevaporated
  8. customThe residue is purified by prep HPLC E

Sources & evidence

ORD record
ord-7a928ac18881410ab4577b4524703fce
Source dataset
uspto-grants-2016_08
Patent number
US09428456B2

Reaction notes

Loading…