Water → 5-(2-Aminopyrimidin-5-yl)-N-(4-(trifluoromethoxy)phenyl)nicotinamide

HRID 629102Notes

Reaction equation

HRID 629102 reaction equation
Br[C:2]1[CH:3]=[N:4][CH:5]=[C:6]([CH:21]=1)[C:7]([NH:9][C:10]1[CH:15]=[CH:14][C:13]([O:16][C:17]([F:20])([F:19])[F:18])=[CH:12][CH:11]=1)=[O:8].CC1(C)C(C)(C)OB([C:30]2[CH:31]=[N:32][C:33]([NH2:36])=[N:34][CH:35]=2)O1.C([O-])([O-])=O.[K+].[K+].O>O1CCOCC1>[NH2:36][C:33]1[N:34]=[CH:35][C:30]([C:2]2[CH:3]=[N:4][CH:5]=[C:6]([CH:21]=2)[C:7]([NH:9][C:10]2[CH:15]=[CH:14][C:13]([O:16][C:17]([F:20])([F:19])[F:18])=[CH:12][CH:11]=2)=[O:8])=[CH:31][N:32]=1

Participants

6

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 46840185-bromo-N-(4-(trifluoromethoxy)phenyl)nicotinamideHCID 177502122-Aminopyrimidine-5-boronic acid, pinacol ester

Product 1

HCID 722035675-(2-Aminopyrimidin-5-yl)-N-(4-(trifluoromethoxy)phenyl)nicotinamide

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

5-Bromo-N-(4-(trifluoromethoxy)phenyl)nicotinamide (Stage 61.1, 181 mg, 0.5 mmol), 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrimidin-2-amine (133 mg, 0.6 mmol), PdCl2(dppf)-(CH2Cl2) (20.42 mg, 0.025 mmol), K2CO3 (138 mg, 1 mmol), water (2 mL) and dioxane (10 mL) were added to a vial, which was sealed, evacuated/purged with argon and the RM was stirred at 90° C. for 24 h. The solvent was evaporated off under reduced pressure and the residue was treated with water and extracted with EtOAc. The combined extracts were dried over Na2SO4 and the solvent was evaporated off under reduced pressure to give the product which was recrystallized from hot EtOAc to afford the title compound as a beige powder. UPLC-MS (Condition 2) tR 0.89 min, m/z=376.2 [M+H]+; 1H-NMR (400 MHz, DMSO-d6) δ ppm 6.98 (s, 2H) 7.41 (d, J=8.99 Hz, 2H) 7.90 (d, J=8.99 Hz, 2H) 8.50-8.55 (m, 1H) 8.76 (s, 2H) 9.00 (d, J=1.95 Hz, 1H) 9.06 (d, J=1.96 Hz, 1H) 10.62 (s, 1H).

Workup

  1. customwas sealed
  2. customevacuated/purged with argon
  3. customThe solvent was evaporated off under reduced pressure
  4. additionthe residue was treated with water
  5. extractionextracted with EtOAc
  6. dry with materialThe combined extracts were dried over Na2SO4
  7. customthe solvent was evaporated off under reduced pressure
  8. customto give the product which
  9. customwas recrystallized from hot EtOAc

Sources & evidence

ORD record
ord-b1b0b8e9abb0484c812bf8f6eb4b19a3
Source dataset
uspto-grants-2016_04
Patent number
US09315489B2

Reaction notes

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