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

HRID 632834Notes

Reaction equation

HRID 632834 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]([C:24]1[CH:29]=[CH:28][C:27](I)=[CH:26][CH:25]=1)([CH3:23])([CH3:22])[CH3:21].CNCCNC.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>CN1C(=O)CCC1.[Cu]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:27]4[CH:28]=[CH:29][C:24]([C:20]([CH3:23])([CH3:22])[CH3:21])=[CH:25][CH:26]=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 1420291-tert-Butyl-4-iodobenzeneHCID 1212495913-(2-amino-7,8-dihydropyrido[4,3-d]pyrimidin-6(5H)-yl)-4-methylpyridin-2(1H)-one

Product 1

HCID 1212495483-(2-amino-7,8-dihydropyrido[4,3-d]pyrimidin-6(5H)-yl)-1-(4-tert-butylphenyl)-4-methylpyridin-2(1H)-oneYield 57%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
70 °C

Procedure

A mixture of 3-(2-amino-7,8-dihydropyrido[4,3-d]pyrimidin-6(5H)-yl)-4-methylpyridin-2(1H)-one, 1-tert-butyl-4-iodobenzene (0.071 mL, 0.40 mmol), N,N′-dimethylethylenediamine (0.022 mL, 0.20 mmol), potassium phosphate tribasic (170 mg, 0.80 mmol), copper (I) iodide (15 mg, 0.080 mmol) in 1.0 mL NMP was heated at 70° C. for 17 hours. The reaction mixture was partitioned between EtOAc and aqueous NaHCO3 solution, the EtOAc layer washed with H2O, brine, dried with anhydrous Na2SO4 and rotary evaporated. The resulting oil was chromatographed eluting with CHCl3, then CHCl3/EtOAc (1:1), and then gradient 3% to 6% MeOH in CHCl3/EtOAc (1:1). The solid obtained was then precipitated from an EtOAc/hexane mixture to give a pale yellow solid (44 mg, 57%). 1H NMR (DMSO) δ: 7.94 (s, 1H), 7.48-7.53 (m, 2H), 7.43 (d, J=6.7 Hz, 1H), 7.27-7.33 (m, 2H), 6.30 (s, 2H), 6.19 (d, J=7.0 Hz, 1H), 3.98 (br. s, 2H), 3.31 (br. s, 2H), 2.68 (t, J=5.3 Hz, 2H), 2.19 (s, 3H), 1.32 (s, 9H)

Workup

  1. customThe reaction mixture was partitioned between EtOAc and aqueous NaHCO3 solution
  2. washthe EtOAc layer washed with H2O, brine
  3. dry with materialdried with anhydrous Na2SO4 and rotary evaporated
  4. customThe resulting oil was chromatographed
  5. washeluting with CHCl3
  6. customThe solid obtained
  7. customwas then precipitated from an EtOAc/hexane mixture

Sources & evidence

ORD record
ord-5a1fc918034c4ffa837926e5e558df51
Source dataset
uspto-grants-2016_04
Patent number
US09321766B1

Reaction notes

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