3-Chloro-1,1-diethoxypropane → 2,4-Diamino-5-(3-(3,3-diethoxypropoxy)-4,5-dimethoxybenzyl)pyrimidine

HRID 280001Notes

Reaction equation

HRID 280001 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+].[CH2:27]([O:29][CH:30]([O:34][CH2:35][CH3:36])[CH2:31][CH2:32]Cl)[CH3:28]>CS(C)=O>[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]([O:20][CH2:32][CH2:31][CH:30]([O:34][CH2:35][CH3:36])[O:29][CH2:27][CH3:28])[CH:11]=2)=[CH:4][N:3]=1

Participants

5

Reactant 3

HCID 962173-Chloro-1,1-diethoxypropaneHCID 128497693-DemethyltrimethoprimHCID 23665647Potassium tert-butoxide

Product 1

HCID 128497702,4-Diamino-5-(3-(3,3-diethoxypropoxy)-4,5-dimethoxybenzyl)pyrimidineYield 83%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

To a solution of 27.6 g, (0.1 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 400 mL of dry dimethyl sulfoxide was added 11.22 g (0.10 mole) of potassium t-butoxide. To the resulting suspension was added dropwise 17.92 g (0.107 mole) of β-chloropropionaldehyde diethylacetal. The mixture was heated at 65° overnight. The solvent was removed under vacuum and the residue was partitioned between 750 mL methylene chloride and 750 mL of 0.1N sodium hydroxide. The organic layer was separated and the aqueous layer was extracted with an additional 750 mL of methylene chloride. The organic layers were combined, washed with 750 mL of water, dried (MgSO4), and purified by flash column chromatography to yield 33.38 g (83%) of the title compound (mp 105°-106.5°). Anal. Calcd for C 20 H30N4O5 : C, 59.10; H, 7.44; N, 13.78. Found: C, 58.71; H, 7.40; N, 13.58.

Workup

  1. temperatureThe mixture was heated at 65° overnight
  2. customThe solvent was removed under vacuum
  3. customthe residue was partitioned between 750 mL methylene chloride and 750 mL of 0.1N sodium hydroxide
  4. customThe organic layer was separated
  5. extractionthe aqueous layer was extracted with an additional 750 mL of methylene chloride
  6. washwashed with 750 mL of water
  7. dry with materialdried (MgSO4)
  8. custompurified by flash column chromatography

Sources & evidence

ORD record
ord-b18fdee0a9664f8aad3d57c575567d7d
Source dataset
uspto-grants-1986_05
Patent number
US04587342

Reaction notes

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