2-Iodotoluene → 3-(2-amino-7,8-dihydropyrido[4,3-d]pyrimidin-6(5H)-yl)-4-methyl-1-(2-methylphenyl)pyridin-2(1H)-one

HRID 632840Notes

Reaction equation

HRID 632840 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.I[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=1[CH3:27].CNCCNC.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:21]4[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=4[CH3:27])[CH:15]=[CH:16][C:17]=3[CH3:18])[CH2:9][CH2:8][C:6]=2[N:7]=1

Participants

7

Reactant 4

HCID 51282-IodotolueneHCID 8070N,N'-DimethylethylenediamineHCID 62657Potassium Phosphate, TribasicHCID 1212495913-(2-amino-7,8-dihydropyrido[4,3-d]pyrimidin-6(5H)-yl)-4-methylpyridin-2(1H)-one

Product 1

HCID 1212495513-(2-amino-7,8-dihydropyrido[4,3-d]pyrimidin-6(5H)-yl)-4-methyl-1-(2-methylphenyl)pyridin-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 (0.025 g, 0.097 mmol), 1-iodo-2-methylbenzene (20 mg, 0.097 mmol), N1,N2-dimethylethane-1,2-diamine (6 mg, 0.049 mmol), copper iodide (5 mg, 0.020 mmol), and potassium phosphate (41 mg, 0.194 mmol) in 0.5 mL of N-methylpyrrolidone was heated to 70° C. After allowing the reaction to stir overnight (17 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 with NaHCO3 (2×10 mL). The crude organic layers were combined, dried over anhydrous Na2SO4 (s), filtered and the concentrated in vacuo. The crude mixture was then purified using the ISCO flash chromatography system using a CHCl3/EtOAc gradient. Upon reaching a 1:1 mixture of EtOAc and CHCl3, 3% MeOH was added and increased up to 6% MeOH. After concentrating the appropriate fractions, a white solid was collected as the pure product (8 mg, 24%). 1H NMR (DMSO) δ: 7.92 (s, 1H), 7.45-7.52 (m, 2H), 7.46 (m, 1H), 7.28-7.35 (m, 2H), 6.28 (s, 2H), 6.17 (m, 1H), 3.96 (br. S, H), 3.29 (s, 2H), 2.66(t, j=5.3 Hz, 2H), 2.21 (s, 3H), 2.07 (s, 3H).

Workup

  1. customthe reaction
  2. temperatureto cool to room temperature
  3. extractionThe reaction was extracted with EtOAc (3×5 mL) and with NaHCO3 (2×10 mL)
  4. dry with materialdried over anhydrous Na2SO4 (s)
  5. filtrationfiltered
  6. concentrationthe concentrated in vacuo
  7. customThe crude mixture was then purified
  8. additiona 1:1 mixture of EtOAc and CHCl3, 3% MeOH
  9. additionwas added
  10. temperatureincreased up to 6% MeOH
  11. concentrationAfter concentrating the appropriate fractions
  12. customa white solid was collected as the pure product (8 mg, 24%)

Sources & evidence

ORD record
ord-9a7d6046fa7148a19172d8b37c472fb6
Source dataset
uspto-grants-2016_04
Patent number
US09321766B1

Reaction notes

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