Sodium Carbonate → N6-(4-{[2-(trifluoromethyl)pyridin-4-yl]oxy}phenyl)-4,5'-bipyrimidine-2,6-diamine

HRID 2244188Notes

Reaction equation

HRID 2244188 reaction equation
C[C:2]1C=CC=[C:4](C)[C:3]=1[C:9]1[N:14]=[C:13]([NH2:15])[N:12]=[C:11]([NH:16][C:17]2[CH:22]=[CH:21][C:20]([O:23][C:24]3[CH:29]=[CH:28][N:27]=[C:26]([C:30]([F:33])([F:32])[F:31])[CH:25]=3)=[CH:19][CH:18]=2)[CH:10]=1.[N:34]1C=C(B(O)O)C=[N:36][CH:35]=1.C(=O)([O-])[O-].[Na+].[Na+]>CN(C=O)C>[F:32][C:30]([F:33])([F:31])[C:26]1[CH:25]=[C:24]([O:23][C:20]2[CH:19]=[CH:18][C:17]([NH:16][C:11]3[N:12]=[C:13]([NH2:15])[N:14]=[C:9]([C:3]4[CH:4]=[N:34][CH:35]=[N:36][CH:2]=4)[CH:10]=3)=[CH:22][CH:21]=2)[CH:29]=[CH:28][N:27]=1

Participants

5

Reactant 3

HCID 10340Sodium CarbonateHCID 2795193(Pyrimidin-5-yl)boronic acidHCID 118449986-(2,6-dimethylphenyl)-N4-(4-{[2-(trifluoromethyl) pyridin-4-yl]oxy}phenyl)pyrimidine-2,4-diamine

Product 1

HCID 11845000N6-(4-{[2-(trifluoromethyl)pyridin-4-yl]oxy}phenyl)-4,5'-bipyrimidine-2,6-diamineYield 23%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A suspension of 6-chloro-N4-(4-{[2-(trifluoromethyl)pyridin-4-yl]oxy}phenyl)pyrimidine-2,4-diamine (150 mg, 0.39 mmol, see example 335), pyrimidin-5-ylboronic acid (97.37 mg, 0.79 mmol), tetrakis(triphenylphosphin)palladium(0) (45.41 mg, 0.04 mmol), sodium carbonate (208.23 mg, 1.96 mmol) in 2.5 mil of anhydrous DMF was degassed for 10 min. The mixture was reacted under microwave condition at 180° C. for 20 min. The reaction mixture was filtered and concentrated. The residue was extracted with EtOAc (6 ml) and washed with 1 M NaOH solution (1 mL×2) and water (1 mL×3). The organic layer was dried to furnish 129 mg of the crude product. The crude product was purified by prep-TLC (Hex:EtOAc=2:8) to give 38 mg (23%) of the title compound as a yellow solid. 1H NMR (CD3OD): δ 9.28 (s, 2H), 9.20 (s, 1H), 8.54 (d, 1H), 7.88 (d, 2H), 7.32 (d, 1H), 7.15 (m, 3H), 6.56 (s, 1H) ppm; MS ES 426 (M+H)+, calc. 426, RT=2.35 min; TLC (Hexane:EtOAc=1:9) Rf=0.25.

Workup

  1. customwas degassed for 10 min
  2. customThe mixture was reacted under microwave condition at 180° C. for 20 min
  3. filtrationThe reaction mixture was filtered
  4. concentrationconcentrated
  5. extractionThe residue was extracted with EtOAc (6 ml)
  6. washwashed with 1 M NaOH solution (1 mL×2) and water (1 mL×3)
  7. customThe organic layer was dried
  8. customto furnish 129 mg of the crude product
  9. customThe crude product was purified by prep-TLC (Hex:EtOAc=2:8)

Sources & evidence

ORD record
ord-bef4fcfb240a4777bb863092c38668c4
Source dataset
uspto-grants-2010_03
Patent number
US07678804B2

Reaction notes

Loading…