N,N'-Dimethylethylenediamine → tert-butyl {4-[3-(2-amino-7,8-dihydropyrido[4,3-d]pyrimidin-6(5H)-yl)-4-methyl-2-oxopyridin-1(2H)-yl]phenyl}carbamate

HRID 632844Notes

Reaction equation

HRID 632844 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.[C:20]([O:24][C:25](=[O:34])[NH:26][C:27]1[CH:32]=[CH:31][C:30](I)=[CH:29][CH:28]=1)([CH3:23])([CH3:22])[CH3:21].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:30]4[CH:29]=[CH:28][C:27]([NH:26][C:25](=[O:34])[O:24][C:20]([CH3:22])([CH3:21])[CH3:23])=[CH:32][CH:31]=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 62657Potassium Phosphate, TribasicHCID 2773612tert-butyl N-(4-iodophenyl)carbamateHCID 1212495913-(2-amino-7,8-dihydropyrido[4,3-d]pyrimidin-6(5H)-yl)-4-methylpyridin-2(1H)-one

Product 1

HCID 121261407tert-butyl {4-[3-(2-amino-7,8-dihydropyrido[4,3-d]pyrimidin-6(5H)-yl)-4-methyl-2-oxopyridin-1(2H)-yl]phenyl}carbamate

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 (250 mg, 0.97 mmol), tert-butyl(4-iodophenyl)carbamate (200 mg, 0.97 mmol), N1,N2-dimethylethane-1,2-diamine (50 mg, 0.49 mmol), copper iodide (40 mg, 0.20 mmol), and potassium phosphate (410 mg, 1.94 mmol) in 2.0 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 2×'s with NaHCO3 (2×10 mL). The crude organic layers were combined, dried over anhydrous Na2SO4, filtered and the concentrated in vacuo. The crude mixture was then purified using the ISCO flash chromatography system using an 0-100% EtOAc/100-0% Hexane gradient mixture. Following concentration of the appropriate fractions the title compound was collected as an off white solid (150 mg, 33%). 1H NMR (DMSO) δ: 9.52 (s, 1H), 7.92 (s, 1H), 7.45-7.52 (m, 2H), 7.41 (d, J=6.7 Hz, 1H), 7.24-7.31 (m, 2H), 6.28 (s, 2H), 6.17 (d, J=7.0 Hz, 1H), 3.96 (br. S, H), 3.29 (s, 2H), 2.66(t, j=5.3 Hz, 2H), 2.18 (s, 3H), 1.39 (s, 9H).

Workup

  1. customthe reaction
  2. temperatureto cool to room temperature
  3. extractionThe reaction was extracted with EtOAc (3×5 mL) and 2×'
  4. dry with materialdried over anhydrous Na2SO4
  5. filtrationfiltered
  6. concentrationthe concentrated in vacuo
  7. customThe crude mixture was then purified
  8. customwas collected as an off white solid (150 mg, 33%)

Sources & evidence

ORD record
ord-1227c361e552445895c330a38aa21cc4
Source dataset
uspto-grants-2016_04
Patent number
US09321766B1

Reaction notes

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