Potassium Phosphate, Tribasic → 3-(2-amino-7,8-dihydropyrido[4,3-d]pyrimidin-6(5H)-yl)-1-(4-methoxyphenyl)-4-methylpyridin-2(1H)-one

HRID 632835Notes

Reaction equation

HRID 632835 reaction equation
[NH2:1][C:2]1[N:3]=[CH:4][C:5]2[CH2:11][N:10]([C:12]3[C:13](=[O:19])[NH:14][CH:15]=[CH:16][C:17]=3[CH3:18])[CH2:9][CH2:8][C:6]=2[N:7]=1.[CH3:20][O:21][C:22]1[CH:27]=[CH:26][C:25](I)=[CH:24][CH:23]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>CN1CCCC1=O.[Cu](I)I>[NH2:1][C:2]1[N:3]=[CH:4][C:5]2[CH2:11][N:10]([C:12]3[C:13](=[O:19])[N:14]([C:25]4[CH:26]=[CH:27][C:22]([O:21][CH3:20])=[CH:23][CH:24]=4)[CH:15]=[CH:16][C:17]=3[CH3:18])[CH2:9][CH2:8][C:6]=2[N:7]=1

Participants

6

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 696764-IodoanisoleHCID 1212495913-(2-amino-7,8-dihydropyrido[4,3-d]pyrimidin-6(5H)-yl)-4-methylpyridin-2(1H)-one

Product 1

HCID 1212495593-(2-amino-7,8-dihydropyrido[4,3-d]pyrimidin-6(5H)-yl)-1-(4-methoxyphenyl)-4-methylpyridin-2(1H)-one

Reagents, catalysts & solvents 2

HCID 83717Copper iodideCatalystHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
70 °C

Procedure

A degassed solution of 3-(2-amino-7,8-dihydropyrido[4,3-d]pyrimidin-6(5H)-yl)-4-methylpyridin-2(1H)-one (25 mg, 0.097 mmol), 4-methoxy-iodobenzene (23 mg, 97 mmol) N1,N2-dimethylethane-1,2-diamine (5 mg, 0.049 mmol), copper iodide (5 mg, 22 mmol), and potassium phosphate (41 mg, 0.194 mmol) in 2 mL of N-methylpyrrolidone was heated to 70° C. After allowing the reaction to stir overnight (19 h) at 70° C., the reaction was complete and allowed to cool to room temperature. The reaction was extracted with EtOAc (3×5 mL) and NaHCO3 (2×10 mL). The crude organic layers were combined, dried over anhydrous Na2SO4 (s), filtered and then concentrated in vacuo. The crude mixture was purified using the ISCO flash chromatography system using a 0-100% EtOAc gradient/100-0% Hexane gradient mixture. Following concentration of the appropriate fractions the crude solid collected was further purified by recrystallization using an Et2O/Hexane solvent mixture to give the title compound as an off white solid (13 mg, 37%). 1H NMR (DMSO) δ: 7.92 (s, 1H), 7.45-7.52 (m, 2H), 7.61 (d, J=6.7 Hz, 1H), 7.24-7.31 (m, 2H), 6.28 (s, 2H), 6.37 (d, J=7.0 Hz, 1H), 3.96 (br. S, H), 3.72 (s, 3H), 3.29 (s, 2H), 2.66(t, j=5.3 Hz, 2H), 2.18 (s, 3H).

Workup

  1. customthe reaction
  2. temperatureto cool to room temperature
  3. extractionThe reaction was extracted with EtOAc (3×5 mL) and NaHCO3 (2×10 mL)
  4. dry with materialdried over anhydrous Na2SO4 (s)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe crude mixture was purified
  8. customcollected
  9. customwas further purified by recrystallization

Sources & evidence

ORD record
ord-97b86923401947d390add892d0811a5b
Source dataset
uspto-grants-2016_04
Patent number
US09321766B1

Reaction notes

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