Dimethylformamide → 4-Chloro-2,6-dimethyl-5-{[2-(trimethylsilyl)ethoxy]methyl}-5H-pyrrolo[3,2-d]pyrimidine-7-carbaldehyde

HRID 1423389Notes

Reaction equation

HRID 1423389 reaction equation
Br[C:2]1[C:6]2[N:7]=[C:8]([CH3:12])[N:9]=[C:10]([Cl:11])[C:5]=2[N:4]([CH2:13][O:14][CH2:15][CH2:16][Si:17]([CH3:20])([CH3:19])[CH3:18])[C:3]=1[CH3:21].C([Li])CCC.CN([CH:30]=[O:31])C>O1CCCC1>[Cl:11][C:10]1[C:5]2[N:4]([CH2:13][O:14][CH2:15][CH2:16][Si:17]([CH3:20])([CH3:19])[CH3:18])[C:3]([CH3:21])=[C:2]([CH:30]=[O:31])[C:6]=2[N:7]=[C:8]([CH3:12])[N:9]=1

Participants

5

Reactant 3

HCID 6228DimethylformamideHCID 866666387-Bromo-4-chloro-2,6-dimethyl-5-{[2-(trimethylsilyl)ethoxy]methyl}-5H-pyrrolo[3,2-d]pyrimidineHCID 178418339Butyllithium

Product 1

HCID 866666394-Chloro-2,6-dimethyl-5-{[2-(trimethylsilyl)ethoxy]methyl}-5H-pyrrolo[3,2-d]pyrimidine-7-carbaldehyde

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

7-Bromo-4-chloro-2,6-dimethyl-5-{[2-(trimethylsilyl)ethoxy]methyl}-5H-pyrrolo[3,2-d]pyrimidine from example A9 (12.41 g; 31.76 mmol) is dissolved in dry tetrahydrofurane (100 mL). At −78° C. n-butyllithium (12.7 mL; 31.76 mmol; 2.5M solution in n-hexane) is syringed into the stirred reaction mixture. After 30 min DMF (12.4 mL; 158.80 mmol) is added via syringe and the mixture is stirred for additional 2 hours at −78° C. and for 30 minutes at 0° C. The reaction is quenched by addition of 1M citric acid (32 mL) and brine (32 mL). After diluting with tert-butylmethylether the aqueous layer is separated and extracted with tert-butylmethylether (3×50 mL). The combined organic layers are dried over MgSO4 and the solvent is removed under reduced pressure. The residue is purified by column chromatography on silica gel (cyclohexane:ethylacetate/7:3) affording the title compound as a white solid.

Workup

  1. customThe reaction is quenched by addition of 1M citric acid (32 mL) and brine (32 mL)
  2. additionAfter diluting with tert-butylmethylether the aqueous layer
  3. customis separated
  4. extractionextracted with tert-butylmethylether (3×50 mL)
  5. dry with materialThe combined organic layers are dried over MgSO4
  6. customthe solvent is removed under reduced pressure
  7. customThe residue is purified by column chromatography on silica gel (cyclohexane:ethylacetate/7:3)

Sources & evidence

ORD record
ord-3aafa3a0ef7e45b5a16733677fbd8025
Source dataset
uspto-grants-2015_01
Patent number
US08927557B2

Reaction notes

Loading…