Potassium Phosphate, Tribasic → HCID 71003455, compound

HRID 2283497Notes

Reaction equation

HRID 2283497 reaction equation
F[C:2]1[N:7]=[CH:6][C:5]([C:8]2[CH:13]=[C:12]([NH2:14])[CH:11]=[C:10]([NH:15][C:16]3[CH:21]=[C:20]([C:22]([F:25])([F:24])[F:23])[CH:19]=[CH:18][N:17]=3)[N:9]=2)=[CH:4][CH:3]=1.[NH2:26][CH:27]1[CH2:31][CH2:30][NH:29][C:28]1=[O:32].P([O-])([O-])([O-])=O.[K+].[K+].[K+].C(N(CC)C(C)C)(C)C>CS(C)=O>[NH2:14][C:12]1[CH:11]=[C:10]([NH:15][C:16]2[CH:21]=[C:20]([C:22]([F:25])([F:24])[F:23])[CH:19]=[CH:18][N:17]=2)[N:9]=[C:8]([C:5]2[CH:6]=[N:7][C:2]([NH:26][CH:27]3[CH2:31][CH2:30][NH:29][C:28]3=[O:32])=[CH:3][CH:4]=2)[CH:13]=1

Participants

6

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 81531DiisopropylethylamineHCID 104868053-Amino-pyrrolidin-2-oneHCID 86731999HCID 86731999, compound

Product 1

HCID 71003455HCID 71003455, compound

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
130 °C

Procedure

6′-Fluoro-N6-[4-(trifluoromethyl)pyridin-2-yl]-2,3′-bipyridine-4,6-diamine (50 mg, 0.143 mmol), 3-aminopyrrolidin-2-one (39.1 mg, 0.286 mmol), tribasic potassium phosphate (60.8 mg, 0.286 mmol), and N,N-diisopropylethylamine (0.050 ml, 0.286 mmol) were dissolved in dimethylsulfoxide (0.5 mL). The mixture was heated to 130° C. with stirring for three days. After allowing to cool to room temperature, the reaction mixture was partitioned between ethyl acetate (30 mL) and saturated aqueous sodium bicarbonate solution (15 mL). The layers were separated, and the organic layer was washed with water (3×5 mL) and brine (10 mL), dried over sodium sulfate, filtered, and concentrated under reduced pressure. The crude residue was purified using reverse phase HPLC (15 to 85% acetonitrile/water with 0.1% TFA gradient). The fractions containing the product were partitioned between 10% isopropanol/chloroform and 1:1 saturated aqueous sodium bicarbonate solution:brine. The layers were separated, and the aqueous layer was extracted with additional 10% isopropanol/chloroform. The combined organic layers were dried over sodium sulfate, filtered, and concentrated under reduced pressure to afford 3-[(4-amino-6-{[4-(trifluoromethyl)pyridin-2-yl]amino}-2,3′-bipyridin-6′-yl)amino]pyrrolidin-2-one. MS ESI calcd. for C20H19F3N7O [M+H]+ 430. found 430. 1H NMR (500 MHz, DMSO-d6) δ 9.74 (s, 1H), 8.62 (s, 1H), 8.50 (d, J=2.2 Hz, 1H), 8.40 (d, J=5.1 Hz, 1H), 7.88 (dd, J=2.4, 8.8 Hz, 1H), 7.83 (s, 1H), 7.08 (d, J=5.3 Hz, 1H), 6.94 (d, J=7.3 Hz, 1H), 6.61 (d, J=8.8 Hz, 1H), 6.53 (d, J=1.6 Hz, 1H), 6.46 (s, 1H), 5.97 (s, 2H), 4.60-4.52 (m, 1H), 3.25-3.20 (m, 2H), 2.52-2.46 (m, 1H), 1.87-1.79 (m, 1H). rhSyk IC50=4 nM.

Workup

  1. temperatureto cool to room temperature
  2. customthe reaction mixture was partitioned between ethyl acetate (30 mL) and saturated aqueous sodium bicarbonate solution (15 mL)
  3. customThe layers were separated
  4. washthe organic layer was washed with water (3×5 mL) and brine (10 mL)
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe crude residue was purified
  9. additionThe fractions containing the product
  10. customwere partitioned between 10% isopropanol/chloroform and 1:1 saturated aqueous sodium bicarbonate solution
  11. customThe layers were separated
  12. extractionthe aqueous layer was extracted with additional 10% isopropanol/chloroform
  13. dry with materialThe combined organic layers were dried over sodium sulfate
  14. filtrationfiltered
  15. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-482b78f301484bbdaefd066a83eea95e
Source dataset
uspto-grants-2015_09
Patent number
US09145391B2

Reaction notes

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