Sodium hydride → 4-Chloro-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo(2,3-d)pyrimidine

HRID 882156Notes

Reaction equation

[Cl:1][C:2]1[C:3]2[CH:10]=[CH:9][NH:8][C:4]=2[N:5]=[CH:6][N:7]=1.[H-].[Na+].[CH3:13][Si:14]([CH2:17][CH2:18][O:19][CH2:20]Cl)([CH3:16])[CH3:15]>O1CCCC1>[Cl:1][C:2]1[C:3]2[CH:10]=[CH:9][N:8]([CH2:20][O:19][CH2:18][CH2:17][Si:14]([CH3:16])([CH3:15])[CH3:13])[C:4]=2[N:5]=[CH:6][N:7]=1

Participants

Conditions

Temperature: 0 °C

Procedure

To a solution of 4-chloro-7H-pyrrolo[2,3-d]pyrimidine (15.3 g, 99.6 mmol) in tetrahydrofuran (200 mL) was added NaH (60% dispersion in mineral oil, 4.20 g, 105 mmol) at 0° C. The resulting solution was stirred for 1 hour at 0° C. and then SEMCl (16.6 g, 100 mmol) was added dropwise. After stirring for an additional 5 hours at 25° C., the reaction was quenched by addition of 250 mL of water/ice, and extracted with ethyl acetate (×2). The organic layers were combined and dried over anhydrous sodium sulfate and concentrated in vacuo. The reaction was purified by chromatography using silica gel, eluting with 50% EtOAc/petroleum ether. The product was collected and concentrated in vacuo to afford 4-chloro-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidine as a light yellow oil. LRMS (PSI) calc'd for C12H19N3ClOSi [M+H]+: 284. found 284.

Workup

stirringAfter stirring for an additional 5 hours at 25° C.
customthe reaction was quenched by addition of 250 mL of water/ice
extractionextracted with ethyl acetate (×2)
dry with materialdried over anhydrous sodium sulfate
concentrationconcentrated in vacuo
customThe reaction was purified by chromatography
washeluting with 50% EtOAc/petroleum ether
customThe product was collected
concentrationconcentrated in vacuo

Sources & evidence

ORD record: ord-345045da54b94a8ebc0b79c3ad3bfde1
Source dataset: uspto-grants-2015_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08993756B2

Reaction notes

Loading…