Dimethyl Sulfoxide → 7-Bromo-4-chloro-2,6-dimethyl-5-{[2-(trimethylsilyl)ethoxy]methyl}-5H-pyrrolo[3,2-d]pyrimidine

HRID 1423388Notes

Reaction equation

HRID 1423388 reaction equation
[H-].[Na+].CS(C)=O.[Br:7][C:8]1[C:12]2[N:13]=[C:14]([CH3:18])[N:15]=[C:16]([Cl:17])[C:11]=2[NH:10][C:9]=1[CH3:19].[CH3:20][Si:21]([CH3:28])([CH3:27])[CH2:22][CH2:23][O:24][CH2:25]Cl>CN(C=O)C.ClCCl>[Br:7][C:8]1[C:12]2[N:13]=[C:14]([CH3:18])[N:15]=[C:16]([Cl:17])[C:11]=2[N:10]([CH2:25][O:24][CH2:23][CH2:22][Si:21]([CH3:28])([CH3:27])[CH3:20])[C:9]=1[CH3:19]

Participants

7

Reactant 4

HCID 679Dimethyl SulfoxideHCID 24758Sodium hydrideHCID 27242712-Chloromethyl 2-(trimethylsilyl)ethyl etherHCID 866666377-Bromo-4-chloro-2,6-dimethyl-5H-pyrrolo[3,2-d]pyrimidine

Product 1

HCID 866666387-Bromo-4-chloro-2,6-dimethyl-5-{[2-(trimethylsilyl)ethoxy]methyl}-5H-pyrrolo[3,2-d]pyrimidine

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 6344DichloromethaneSolvent

Procedure

Sodium hydride (1.82 g; 45.60 mmol; 60% in oil, washed with hexane), is suspended in dry DMF (125 mL) and dry DMSO (25 mL). To the stirring suspension 7-Bromo-4-chloro-2,6-dimethyl-5H-pyrrolo[3,2-d]pyrimidine from example A8 (10.00 g; 38.00 mmol) dissolved in dry DMF (125 mL) is added dropwise within 30 minutes at ambient temperature. After complete addition the reaction mixture is stirred for one hour at ambient temperature. To the resulting solution 2-(trimethylsilyl)ethoxymethylchloride (8.74 mL; 49.40 mmol) is added dropwise and the reaction mixture is stirred for one hour at ambient temperature. After diluting with water/ice and dichloromethane, the organic layer is separated and the aqueous layer is extracted with dichloromethane (2×400 mL). The combined organic layers are dried over MgSO4 and filtered through a plug of neutral alumina (act. 2-3). The solvent is removed under reduced pressure and the residue is purified by column chromatography on silica gel (cyclohexane:ethylacetate/9:1) affording the title compound as a white solid.

Workup

  1. additionis added dropwise within 30 minutes at ambient temperature
  2. additionAfter complete addition the reaction mixture
  3. stirringthe reaction mixture is stirred for one hour at ambient temperature
  4. customthe organic layer is separated
  5. extractionthe aqueous layer is extracted with dichloromethane (2×400 mL)
  6. dry with materialThe combined organic layers are dried over MgSO4
  7. filtrationfiltered through a plug of neutral alumina (act. 2-3)
  8. customThe solvent is removed under reduced pressure
  9. customthe residue is purified by column chromatography on silica gel (cyclohexane:ethylacetate/9:1)

Sources & evidence

ORD record
ord-00ef3a486fad4914a59bff10e0223fd3
Source dataset
uspto-grants-2015_01
Patent number
US08927557B2

Reaction notes

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