Potassium Carbonate → HCID 58174211, compound

HRID 339803Notes

Reaction equation

HRID 339803 reaction equation
Br[C:2]1[CH:3]=[C:4]([CH2:19][CH2:20][NH:21][C:22]2[C:31]3[C:26](=[N:27][CH:28]=[CH:29][N:30]=3)[N:25]=[CH:24][N:23]=2)[CH:5]=[CH:6][C:7]=1[O:8][C:9]1[CH:14]=[C:13]([C:15]([F:18])([F:17])[F:16])[CH:12]=[CH:11][N:10]=1.[CH:32]1C=CC(P(C2C=CC=CC=2)CCCCP(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[C:62]([O-:65])([O-])=[O:63].[K+].[K+]>CO.CC([O-])=O.CC([O-])=O.[Pd+2]>[N:25]1[C:26]2[C:31](=[N:30][CH:29]=[CH:28][N:27]=2)[C:22]([NH:21][CH2:20][CH2:19][C:4]2[CH:5]=[CH:6][C:7]([O:8][C:9]3[CH:14]=[C:13]([C:15]([F:18])([F:17])[F:16])[CH:12]=[CH:11][N:10]=3)=[C:2]([CH:3]=2)[C:62]([O:65][CH3:32])=[O:63])=[N:23][CH:24]=1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 821241,4-Bis(diphenylphosphino)butaneHCID 58174172HCID 58174172, compound

Product 1

HCID 58174211HCID 58174211, compoundYield 23.4%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 887MethanolSolvent

Conditions

Temperature
110 °C

Procedure

To a solution of {2-[3-bromo-4-(4-trifluoromethylpyridin-2-yloxy)-phenyl]-ethyl}-pteridin-4-yl-amine (243 mg, 0.5 mmol), in methanol in a 45 mL Parr bomb was added Pd(OAc)2 (5.6 mg, 0.25 mmol), DPPB (21 mg, 0.5 mmol), and K2CO3 (138 mg, 1 mmol). The reactor was sealed and charged with 300 psi of CO. The reaction was heated to 110° C. for 15 h, cooled to ambient temperature, filtered through Celite, and concentrated in vacuo. The residue was dissolved in CH2Cl2, washed with H2O, brine, dried over Na2SO4, suction filtered and concentrated in vacuo. The residue was slurried in Et2O and pentane. The solvent was decanted to leave 5-[2-(pteridin-4-ylamino)-ethyl]-2-(4-trifluoromethylpyridin-2-yloxy)-benzoic acid, methyl ester (55 mg; 23% yield) as a light yellow solid: mp 171-172° C.; 1H NMR (300 MHz, CDCl3) δ 9.04 (d, J=2.0 Hz, 1H), 8.84 (s, 1H), 8.64 (d, J=1.9 Hz, 1H), 8.23 (d, J=5.0 Hz, 1H), 7.94 (d, J=2.3 Hz, 1H), 7.52 (dd, J=8.2, 2.2 Hz, 1H), 7.26-7.12 (m, 4H), 4.02 (dd, J=13.7, 6.9 Hz, 2H), 3.67 (s, 3H), 3.13 (t, J=7.3 Hz, 2H); ESIMS m/z 471.

Workup

  1. customThe reactor was sealed
  2. additioncharged with 300 psi of CO
  3. temperaturecooled to ambient temperature
  4. filtrationfiltered through Celite
  5. concentrationconcentrated in vacuo
  6. dissolutionThe residue was dissolved in CH2Cl2
  7. washwashed with H2O, brine
  8. dry with materialdried over Na2SO4, suction
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customThe solvent was decanted

Sources & evidence

ORD record
ord-563b883c0c7e466e818ff701b9e142fb
Source dataset
uspto-grants-2014_11
Patent number
US08895568B2

Reaction notes

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