Pyridine → 1,2,3,4-Tetrahydro-6-methyl-4-(3-nitrophenyl)-3-(1-oxopropyl)-2-oxo-5-pyrimidinecarboxylic acid, ethyl ester

HRID 1590297Notes

Reaction equation

HRID 1590297 reaction equation
C[O:2][C:3]1[NH:4][C:5]([CH3:23])=[C:6]([C:18]([O:20][CH2:21][CH3:22])=[O:19])[CH:7]([C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([N+:15]([O-:17])=[O:16])[CH:10]=2)[N:8]=1.N1C=CC=CC=1.[C:30](Cl)(=[O:33])[CH2:31][CH3:32]>ClCCl>[CH3:23][C:5]1[NH:4][C:3](=[O:2])[N:8]([C:30](=[O:33])[CH2:31][CH3:32])[CH:7]([C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([N+:15]([O-:17])=[O:16])[CH:10]=2)[C:6]=1[C:18]([O:20][CH2:21][CH3:22])=[O:19]

Participants

5

Reactant 3

HCID 1049PyridineHCID 62324Propionyl chlorideHCID 139125831,4-Dihydro-2-methoxy-6-methyl-4-(3-nitrophenyl)-5-pyrimidinecarboxylic acid, ethyl ester

Product 1

HCID 867467161,2,3,4-Tetrahydro-6-methyl-4-(3-nitrophenyl)-3-(1-oxopropyl)-2-oxo-5-pyrimidinecarboxylic acid, ethyl esterYield 66.8%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of 1,4-dihydro-2-methoxy-6-methyl-4-(3-nitrophenyl)-5-pyrimidinecarboxylic acid, ethyl ester (750 mg., 2.35 mmole) and dry pyridine (0.57 ml., 7.05 mmole) in dichloromethane (5.0 ml.) at -20° (methanol/ice bath) under argon is treated dropwise via gas-tight syringe with propionyl chloride (0.26 ml., 2.82 mmole). The reaction mixture is stirred for 2.0 hours and evaporated. The solid yellow residue is dissolved in methanol (25 ml.) and tetrahydrofuran (15 ml.) and treated with 5N hydrochloric acid (6.0 ml.). After stirring at room temperature for 1.0 hour, the reaction mixture is evaporated. The residue is partitioned between ethyl acetate and sodium bicarbonate solution. The organic phase is washed with saturated sodium chloride, dried over magnesium sulfate, and evaporated. The residue is flash chromatographed to give the title compound as a white foam (567 mg.). This foam is combined with material from another batch (290 mg.) and recrystallized from dichloromethane/isopropyl ether to give large shiny white crystals (784 mg., m. p. 152°-154°). TLC(silica gel; 50% ethyl acetate:hexanes) Rf =0.57.

Workup

  1. customevaporated
  2. dissolutionThe solid yellow residue is dissolved in methanol (25 ml.)
  3. additiontetrahydrofuran (15 ml.) and treated with 5N hydrochloric acid (6.0 ml.)
  4. stirringAfter stirring at room temperature for 1.0 hour
  5. customthe reaction mixture is evaporated
  6. customThe residue is partitioned between ethyl acetate and sodium bicarbonate solution
  7. washThe organic phase is washed with saturated sodium chloride
  8. dry with materialdried over magnesium sulfate
  9. customevaporated
  10. customchromatographed

Sources & evidence

ORD record
ord-9305f485926a481a8b70b925d24836c3
Source dataset
uspto-grants-1993_04
Patent number
US05202330

Reaction notes

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