Trifluoroacetic acid → 3-(2-amino-7,8-dihydropyrido[4,3-d]pyrimidin-6(5H)-yl)-1-(4-aminophenyl)-4-methylpyridin-2(1H)-one

HRID 632845Notes

Reaction equation

HRID 632845 reaction equation
[NH2:1][C:2]1[N:3]=[CH:4][C:5]2[CH2:11][N:10]([CH:12]3[C:17](=[O:18])[N:16]([C:19]4[CH:24]=[CH:23][C:22]([NH:25]C(=O)OC(C)(C)C)=[CH:21][CH:20]=4)[CH2:15][CH:14]=[C:13]3[CH3:33])[CH2:9][CH2:8][C:6]=2[N:7]=1.C(O)(C(F)(F)F)=O.C([O-])(O)=O.[Na+]>CO.C1COCC1>[NH2:1][C:2]1[N:3]=[CH:4][C:5]2[CH2:11][N:10]([C:12]3[C:17](=[O:18])[N:16]([C:19]4[CH:20]=[CH:21][C:22]([NH2:25])=[CH:23][CH:24]=4)[CH:15]=[CH:14][C:13]=3[CH3:33])[CH2:9][CH2:8][C:6]=2[N:7]=1

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acid2×HCID 516892Sodium BicarbonateHCID 131735469tert-butyl (4-(5-(2-amino-7,8-dihydropyrido[4,3-d]pyrimidin-6(5H)-yl)-4-methyl-6-oxo-5,6-dihydropyridin-1(2H)-yl)phenyl)carbamate

Product 1

HCID 1212496053-(2-amino-7,8-dihydropyrido[4,3-d]pyrimidin-6(5H)-yl)-1-(4-aminophenyl)-4-methylpyridin-2(1H)-oneYield 88%

Reagents, catalysts & solvents 1

HCID 21899815MeOH tetrahydrofuranSolvent

Procedure

Tert-butyl (4-(5-(2-amino-7,8-dihydropyrido[4,3-d]p yrimidin-6(5H)-yl)-4-methyl-6-oxo-5,6-dihydropyridin-1(2H)-yl)phenyl)carbamate (150 mg, 0.334 mmol) was dissolved into a 1:1 mixture of MeOH/THF (˜10 mL) and treated with CF3COOH drop wise and the reaction was allowed to stir for 4 h. One the reaction was completed, the residual CF3COOH was neutralized with NaHCO3 (aq). The reaction was then extracted with EtOAc (3×10 mL) and brine (˜10 mL). The combined organic layers were dried over anhydrous Na2SO4, filtered and then concentrated in vacuo. The crude organic oil was then purified via column chromatography (MeOH/CHCl3 gradient). Concentration of the appropriate fractions provided the title compound (102 mg, 88%). 1H NMR (DMSO) δ: 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).

Workup

  1. extractionThe reaction was then extracted with EtOAc (3×10 mL) and brine (˜10 mL)
  2. dry with materialThe combined organic layers were dried over anhydrous Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customThe crude organic oil was then purified via column chromatography (MeOH/CHCl3 gradient)

Sources & evidence

ORD record
ord-d8a8a528edae4ee5888b895b3f8b2300
Source dataset
uspto-grants-2016_04
Patent number
US09321766B1

Reaction notes

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