Tetrahydrofuran → N-{4-[3-(2-amino-7,8-dihydropyrido[4,3-d]pyrimidin-6(5H)-yl)-4-methyl-2-oxopyridin-1(2H)-yl]phenyl}-3-methyl-2-furamide

HRID 632846Notes

Reaction equation

HRID 632846 reaction equation
[NH2:1][C:2]1[N:3]=[CH:4][C:5]2[CH2:11][N:10]([C:12]3[C:13](=[O:26])[N:14]([C:19]4[CH:24]=[CH:23][C:22]([NH2:25])=[CH:21][CH:20]=4)[CH:15]=[CH:16][C:17]=3[CH3:18])[CH2:9][CH2:8][C:6]=2[N:7]=1.C1COCC1.[CH3:32][C:33]1[CH:37]=[CH:36][O:35][C:34]=1[C:38](Cl)=[O:39]>CCN(CC)CC>[NH2:1][C:2]1[N:3]=[CH:4][C:5]2[CH2:11][N:10]([C:12]3[C:13](=[O:26])[N:14]([C:19]4[CH:20]=[CH:21][C:22]([NH:25][C:38]([C:34]5[O:35][CH:36]=[CH:37][C:33]=5[CH3:32])=[O:39])=[CH:23][CH:24]=4)[CH:15]=[CH:16][C:17]=3[CH3:18])[CH2:9][CH2:8][C:6]=2[N:7]=1

Participants

5

Reactant 3

HCID 8028TetrahydrofuranHCID 27966743-Methylfuran-2-carbonyl chlorideHCID 1212496053-(2-amino-7,8-dihydropyrido[4,3-d]pyrimidin-6(5H)-yl)-1-(4-aminophenyl)-4-methylpyridin-2(1H)-one

Product 1

HCID 121249568N-{4-[3-(2-amino-7,8-dihydropyrido[4,3-d]pyrimidin-6(5H)-yl)-4-methyl-2-oxopyridin-1(2H)-yl]phenyl}-3-methyl-2-furamide

Reagents, catalysts & solvents 1

HCID 8471TriethylamineSolvent

Conditions

Temperature
40 °C

Procedure

A solution of 3-(2-amino-7,8-dihydropyrido[4,3-d]pyrimidin-6(5H)-yl)-1-(4-aminophenyl)-4-methylpyridin-2(1H)-one (25 mg, 0.075 mmol) in2 mL of THF under N2(g) containing 3 mL of NEt3 was treated with 3-methylfuran-2-carbonyl chloride (13 mg, 0.090 mmol). The reaction mixture was heated to 40° C. and allowed to stir for 3 h. The reaction was cooled and then extracted with EtOAc (3ט10 mL) and water (˜10 mL). The combined organic layers were then washed with ˜20 mL of NaHCO3 (aq). The organic layers were then dried over anhydrous Na2SO4, filtered and then concentrated in vacuo. The crude mixture was purified over silica (EtOAc/Hexanes gradient). Following concentration of the appropriate fractions the title compound was collected as a grey solid (25 mg, 76%). 1H NMR (DMSO) δ: 9.52 (s, 1H), 7.92 (s, 1H), 7.81 (d, J=5.6 Hz, 1H), 7.45-7.52 (m, 2H), 7.41 (d, J=6.7 Hz, 1H), 7.24-7.31 (m, 2H), 6.65 (d, J=5.6 Hz, 1H), 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), 2.35 (s, 3H), 2.18 (s, 3H).

Workup

  1. temperatureThe reaction was cooled
  2. extractionextracted with EtOAc (3ט10 mL) and water (˜10 mL)
  3. washThe combined organic layers were then washed with ˜20 mL of NaHCO3 (aq)
  4. dry with materialThe organic layers were then dried over anhydrous Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe crude mixture was purified over silica (EtOAc/Hexanes gradient)
  8. customwas collected as a grey solid (25 mg, 76%)

Sources & evidence

ORD record
ord-a1bb3259306947a2aa1af2ed6400d755
Source dataset
uspto-grants-2016_04
Patent number
US09321766B1

Reaction notes

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