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

HRID 632839Notes

Reaction equation

HRID 632839 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][C:24]([CH3:27])=[CH:23][CH:22]=1.CNCCNC.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>[Cu](I)I.CN1CCCC1=O>[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][C:24]([CH3:27])=[CH:23][CH:22]=4)[CH:15]=[CH:16][C:17]=3[CH3:18])[CH2:9][CH2:8][C:6]=2[N:7]=1

Participants

7

Reactant 4

HCID 8070N,N'-DimethylethylenediamineHCID 122074-IodotolueneHCID 62657Potassium Phosphate, TribasicHCID 1212495913-(2-amino-7,8-dihydropyrido[4,3-d]pyrimidin-6(5H)-yl)-4-methylpyridin-2(1H)-one

Product 1

HCID 1212495813-(2-amino-7,8-dihydropyrido[4,3-d]pyrimidin-6(5H)-yl)-4-methyl-1-(4-methylphenyl)pyridin-2(1H)-oneYield 38.6%

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), 1-iodo-4-methylbenzene (20 mg, 0.097 mmol), N1,N2-dimethylethane-1,2-diamine (5 mg, 0.049 mmol), Copper Iodide (5 mg, 0.024 mmol), and Potassium Phosphate (41 mg, 0.194 mmol) 2 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 then 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 to 6% MeOH which, after concentrating the appropriate fractions afforded the title compound as a tan solid (13 mg, 38%). 1H NMR (DMSO) δ: 7.90 (s, 1H), 7.50-7.59 (m, 2H), 7.44 (d, J=6.7 Hz, 1H), 7.25-7.32 (m, 2H), 6.19 (s, 2H), 6.08 (d, J=7.0 Hz, 1H), 3.89 (br. S, H), 3.29 (s, 2H), 2.64(t, j=5.3 Hz, 2H), 2.13 (s, 3H), 1.99 (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. concentrationconcentrated 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 to 6% MeOH which
  11. concentrationafter concentrating the appropriate fractions

Sources & evidence

ORD record
ord-2421cfb4b8ba467bb18aa423ac8d297d
Source dataset
uspto-grants-2016_04
Patent number
US09321766B1

Reaction notes

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