Methyl 4-(aminomethyl)benzoate → methyl 4-[(4-hydroxy-2-methyl-6-oxopyrimidin-1(6H)-yl)methyl]benzoate

HRID 1713200Notes

Reaction equation

HRID 1713200 reaction equation
C1C2C(=CC=CC=2)C=CC=1CS/[C:13](=[N:15]\[C:16](=[O:22])[CH2:17][C:18](OC)=[O:19])/[CH3:14].[CH3:23][O:24][C:25](=[O:34])[C:26]1[CH:31]=[CH:30][C:29]([CH2:32][NH2:33])=[CH:28][CH:27]=1>C1COCC1>[OH:22][C:16]1[N:15]=[C:13]([CH3:14])[N:33]([CH2:32][C:29]2[CH:30]=[CH:31][C:26]([C:25]([O:24][CH3:23])=[O:34])=[CH:27][CH:28]=2)[C:18](=[O:19])[CH:17]=1

Participants

4

Reactant 2

HCID 571728Methyl 4-(aminomethyl)benzoateHCID 178500944HCID 178500944, compound

Product 1

HCID 135737356methyl 4-[(4-hydroxy-2-methyl-6-oxopyrimidin-1(6H)-yl)methyl]benzoateYield 20.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of methyl 3-({(1Z)-1-[(2-naphthylmethyl)thio]ethylidene}amino)-3-oxopropanoate (1.9 g, 0.006 mol, from step 1) in THF (25.0 mL), at 0° C., is added methyl-4-aminomethylbenzoate (1.1 g, 0.0067 mol). The reaction mixture is stirred at room temperature for 1 hour, and then concentrated to dryness. The resulting residue is dissolved in dioxane (20.0 mL), DBU (0.1 mL) is added, and the resulting reaction mixture is heated at 70° C. for 1 h under an argon atmosphere. After removing the solvent under reduced pressure, the residue is purified by reverse-phase HPLC using 10-90% CH3CN/Water gradient (40 min) at a flow rate of 80 mL/min. The appropriate fractions (MH+, m/z=275) are combined and freeze-dried to afford the title compound (0.33 g) as a white powder: 1H NMR (CD3OD/400 MHz) δ 7.99 (d 2H, J=8.4 Hz), 7.29 (d, 2H, J=8.4 Hz), 5.42 (s, 1H), 5.36 (s, 2H), 3.88 (s, 3H), and 2.42 (s, 3H); ES-HRMS m/z 275.1021 (M+H calcd for C14H15N2O4 requires 275.1026).

Workup

  1. concentrationconcentrated to dryness
  2. dissolutionThe resulting residue is dissolved in dioxane (20.0 mL)
  3. additionDBU (0.1 mL) is added
  4. customthe resulting reaction mixture
  5. temperatureis heated at 70° C. for 1 h under an argon atmosphere
  6. customAfter removing the solvent under reduced pressure
  7. customthe residue is purified by reverse-phase
  8. custom10-90% CH3CN/Water gradient (40 min)
  9. customfreeze-dried

Sources & evidence

ORD record
ord-82ba1d44e82c447096df50c7a63bd86c
Source dataset
uspto-grants-2010_09
Patent number
US07795271B2

Reaction notes

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