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

HRID 632837Notes

Reaction equation

HRID 632837 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:25]=[CH:24][N:23]([CH3:26])[N: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]([CH:12]3[C:17]([CH3:18])=[CH:16][CH2:15][N:14]([C:21]4[CH:25]=[CH:24][N:23]([CH3:26])[N:22]=4)[C:13]3=[O:19])[CH2:9][CH2:8][C:6]=2[N:7]=1

Participants

7

Reactant 4

HCID 8070N,N'-DimethylethylenediamineHCID 62657Potassium Phosphate, TribasicHCID 133340573-Iodo-1-methyl-1H-pyrazoleHCID 1212495913-(2-amino-7,8-dihydropyrido[4,3-d]pyrimidin-6(5H)-yl)-4-methylpyridin-2(1H)-one

Product 1

HCID 1212495783-(2-amino-7,8-dihydropyrido[4,3-d]pyrimidin-6(5H)-yl)-4-methyl-1-(1-methyl-1H-pyrazol-3-yl)-1,6-dihydropyridin-2(3H)-oneYield 52%

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 (27 mg, 0.100 mmol), 3-iodo-1-methyl-1H-pyrazole (20 mg, 0.097 mmol), N1,N2-dimethylethane-1,2-diamine (5 mg, 0.049 mmol), copper iodide (4 mg, 0.020 mmol), and potassium phosphate (43 mg, 0.197 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 3×'s with EtOAc (3×5 mL) and 2×'s with NaHCO3 (3×10 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 0-100% EtOAc/100-0% Hexane gradient mixture. A second column was done on the impure product using a gradient of MeOH/CHCl3 after which, the appropriate fractions were concentrated, to afford a yellow solid (17 mg, 52%). 1H NMR (DMSO) δ: 8.01 (s, 1H), 7.79 (d, J=6.0, 1H), 6.34 (d, J=6.0, 1H), 6.24 (m, 1H), 6.15 (d, J=7.0 Hz, 2H), 4.00 (br. S, 2H), 3.22 (s, 2H), 2.64(t, j=5.3 Hz, 2H), 2.20 (s, 3H)

Workup

  1. customthe reaction
  2. temperatureto cool to room temperature
  3. extractionThe reaction was extracted 3×'
  4. dry with materialdried over anhydrous Na2SO4 (s)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe crude mixture was then purified
  8. concentrationthe appropriate fractions were concentrated

Sources & evidence

ORD record
ord-046a6c6a2c2b401183f8dc36eeaf5f8c
Source dataset
uspto-grants-2016_04
Patent number
US09321766B1

Reaction notes

Loading…