4-Methyloxybenzyl chloride → 1,4-Dihydro-2-[[(4-methoxyphenyl)methyl]thio]-6-methyl-4-(3-nitrophenyl)-5-pyrimidinecarboxylic acid

HRID 1722408Notes

Reaction equation

HRID 1722408 reaction equation
[CH3:1][C:2]1[NH:7][C:6](=[S:8])[NH:5][CH:4]([C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([N+:15]([O-:17])=[O:16])[CH:10]=2)[C:3]=1[C:18]([O:20]C(C)C)=[O:19].[CH3:24][O:25][C:26]1[CH:33]=[CH:32][C:29]([CH2:30]Cl)=[CH:28][CH:27]=1>O1CCCC1.CCOCC>[CH3:24][O:25][C:26]1[CH:33]=[CH:32][C:29]([CH2:30][S:8][C:6]2[NH:7][C:2]([CH3:1])=[C:3]([C:18]([OH:20])=[O:19])[CH:4]([C:9]3[CH:14]=[CH:13][CH:12]=[C:11]([N+:15]([O-:17])=[O:16])[CH:10]=3)[N:5]=2)=[CH:28][CH:27]=1

Participants

5

Reactant 2

HCID 699934-Methyloxybenzyl chloride2×HCID 2748290Isopropyl 6-methyl-4-(3-nitrophenyl)-2-thioxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate

Product 1

HCID 197695391,4-Dihydro-2-[[(4-methoxyphenyl)methyl]thio]-6-methyl-4-(3-nitrophenyl)-5-pyrimidinecarboxylic acid

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

(-)-1,2,3,4-Tetrahydro-6-methyl-4-(3-nitrophenyl)-2-thioxo-5-pyrimidinecarboxylic acid, 1-methylethyl ester (2.6 mmol, 884 mg) was dissolved in dry tetrahydrofuran and cooled to 0° C. 4-Methoxybenzyl chloride (1.1 eq, 32.9 mmol, 393 μl) was added dropwise. After the addition was complete, the bath was removed and the reaction stirred at room temperature for two hours. The mixture was then heated at 65° C. for 16 hours. TLC 35:65:acetone:hexane showed an incomplete reaction, so additional 4-methoxybenzyl chloride (1.1 eq, 1.3 mmol, 393 μl) was added to the mixture. After 7 hours at 65° C., the mixture was allowed to come to room temperature and diluted with ether. As the mixture cooled to 0° C., a white solid formed. The solid was collected by suction filtration, washed with ether, and dried to afford 1,4-dihydro-2-[[(4-methoxyphenyl)methyl]thio]-6-methyl-4-(3-nitrophenyl)-5-pyrimidinecarboxylic acid, 1-methylether ester hydrochloride, 636 mg (49%).

Workup

  1. additionAfter the addition
  2. customthe bath was removed
  3. temperatureThe mixture was then heated at 65° C. for 16 hours
  4. customan incomplete reaction
  5. waitAfter 7 hours at 65° C.
  6. customto come to room temperature
  7. temperatureAs the mixture cooled to 0° C.
  8. customa white solid formed
  9. filtrationThe solid was collected by suction filtration
  10. washwashed with ether
  11. customdried

Sources & evidence

ORD record
ord-3d1db858f6c044b484be43c46d8f59e5
Source dataset
uspto-grants-1989_08
Patent number
US04855301

Reaction notes

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