3-Chloro-2-butanone → 2,4-Diamino-5-(3,4-dimethoxy-5-(1-methyl-2-oxopropoxy)benzyl)pyrimidine

HRID 280697Notes

Reaction equation

HRID 280697 reaction equation
[NH2:1][C:2]1[N:7]=[C:6]([NH2:8])[C:5]([CH2:9][C:10]2[CH:15]=[C:14]([O:16][CH3:17])[C:13]([O:18][CH3:19])=[C:12]([OH:20])[CH:11]=2)=[CH:4][N:3]=1.CC(C)([O-])C.[K+].Cl[CH:28]([CH3:32])[C:29](=[O:31])[CH3:30]>CS(C)=O>[NH2:1][C:2]1[N:7]=[C:6]([NH2:8])[C:5]([CH2:9][C:10]2[CH:11]=[C:12]([O:20][CH:28]([CH3:32])[C:29](=[O:31])[CH3:30])[C:13]([O:18][CH3:19])=[C:14]([O:16][CH3:17])[CH:15]=2)=[CH:4][N:3]=1

Participants

5

Reactant 3

HCID 200263-Chloro-2-butanoneHCID 128497693-DemethyltrimethoprimHCID 23665647Potassium tert-butoxide

Product 1

HCID 233211222,4-Diamino-5-(3,4-dimethoxy-5-(1-methyl-2-oxopropoxy)benzyl)pyrimidineYield 103.4%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

To a solution of 2.76 g (0.01 mole) of 2,4-diamino-5-(3-hydroxy-4,5-dimethoxybenzyl)pyrimidine (D. E. Schwartz, W. Vetter, and G. Englert, Arzneim.-Forsch. (Drug Res.) 1970, 20, 1867; G. Rey-Bellet and R. Reiner, Helv. Chim. Acta 1970, 53, 945) in 40 mL of dry dimethyl sulfoxide was added 1.12 g (0.01 mole) of potassium t-butoxide. To the resulting suspension was added in one portion 1.16 g (0.0109 mole) of 3-chloro-2-butanone. The mixture was stirred at room temperature for 1 hour. The solvent was removed under vacuum and the residue was partitioned between 100 mL of methylene chloride and 100 mL of 0.1N sodium hydroxide. The organic layer was separated and the aqueous layer was extracted with an additional 100 mL of methylene chloride. The organic layers were combined, washed with 100 mL of water, dried (MgSO4) and concentrated to give a quantitative yield (3.58 g) of the title compound. Recrystallization from 95% ethanol gave an analytical sample; mp 167.5°-168.5°. Anal. Calc'd for C17H22N4O4 : C, 58.95; H, 6.40; N, 16.17. Found: C, 58.77; H, 6.42; N, 16.13.

Workup

  1. customThe solvent was removed under vacuum
  2. customthe residue was partitioned between 100 mL of methylene chloride and 100 mL of 0.1N sodium hydroxide
  3. customThe organic layer was separated
  4. extractionthe aqueous layer was extracted with an additional 100 mL of methylene chloride
  5. washwashed with 100 mL of water
  6. dry with materialdried (MgSO4)
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-f4e823ca4563425b917e2900a33a99d5
Source dataset
uspto-grants-1986_05
Patent number
US04590271

Reaction notes

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