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

HRID 632849Notes

Reaction equation

HRID 632849 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)-one

Reagents, catalysts & solvents 1

HCID 21899815MeOH tetrahydrofuranSolvent

Procedure

A solution of tert-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 (112 mg, 0.334 mmol) in a 1:1 mixture of MeOH/THF (˜10 mL) was treated dropwise with CF3COOH 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 (3ט10 mL) and brine (˜10 mL). The combined organic layers were dried over anhydrous Na2SO4 (s), filtered and the concentrated in vacuo. The crude organic oil was then purified via column chromatography (MeOH/CHCl3 gradient). Following concentration of the appropriate fractions the title compound was isolated (112 mg, 88%). 1H NMR (DMSO) δ: 7.91 (s, 1H), 7.80(m, 1H), 7.41-7.52 (m, 2H), 7.41 (m, 1H), 7.26-7.32 (m, 2H), 6.65(m, 1H), 6.23 (s, 2H), 6.14 (m, 1H), 4.00 (br. s, H), 3.24 (s, 2H), 2.67 (t, J=5.3 Hz, 2H), 2.34 (s, 3H), 2.22 (s, 3H).

Workup

  1. extractionThe reaction was then extracted with EtOAc (3ט10 mL) and brine (˜10 mL)
  2. dry with materialThe combined organic layers were dried over anhydrous Na2SO4 (s)
  3. filtrationfiltered
  4. concentrationthe concentrated in vacuo
  5. customThe crude organic oil was then purified via column chromatography (MeOH/CHCl3 gradient)
  6. customwas isolated (112 mg, 88%)

Sources & evidence

ORD record
ord-dc50e85774e64955be9d987ce32461c8
Source dataset
uspto-grants-2016_04
Patent number
US09321766B1

Reaction notes

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