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

HRID 729984Notes

Reaction equation

HRID 729984 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-e612fd65131542c58fc53f7ae8c9b6c5
Source dataset
uspto-grants-2009_09
Patent number
US07582646B2

Reaction notes

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