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

HRID 632838Notes

Reaction equation

HRID 632838 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]=[C:23]([CH3:27])[CH:22]=1.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]([CH:12]3[C:17]([CH3:18])=[CH:16][CH2:15][N:14]([C:21]4[CH:22]=[C:23]([CH3:27])[CH:24]=[CH:25][CH:26]=4)[C:13]3=[O:19])[CH2:9][CH2:8][C:6]=2[N:7]=1

Participants

7

Reactant 4

HCID 8070N,N'-DimethylethylenediamineHCID 122683-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 1212495523-(2-amino-7,8-dihydropyrido[4,3-d]pyrimidin-6(5H)-yl)-4-methyl-1-(m-tolyl)-1,6-dihydropyridin-2(3H)-oneYield 47.7%

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 (24 mg, 0.096 mmol), 1-iodo-3-methylbenzene (20 mg, 0.097 mmol), N1,N2-dimethylethane-1,2-diamine (5 mg, 0.049 mmol), copper iodide (5 mg, 0.022 mmol), and potassium phosphate (44 mg, 0.199 mmol) in 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 pale yellow solid (16 mg, 47%). 1H NMR (DMSO) δ: 7.99 (s, 1H), 7.80 (d, J=6.0, 1H), 6.56 (d, J=6.0, 1H), 6.28 (m, 1H), 6.20 (d, J=7.0 Hz, 2H), 3.99 (br. S, 2H), 3.31 (s, 2H), 2.66(t, j=5.3 Hz, 2H), 2.15 (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-d18393787a1547f6b73520106699f74e
Source dataset
uspto-grants-2016_04
Patent number
US09321766B1

Reaction notes

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