Sodium hydride → ethyl 4-chloro-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidine-5-carboxylate

HRID 882111Notes

Reaction equation

[Cl:1][C:2]1[C:3]2[C:10]([C:11]([O:13][CH2:14][CH3:15])=[O:12])=[CH:9][NH:8][C:4]=2[N:5]=[CH:6][N:7]=1.[CH3:16][Si:17]([CH2:20][CH2:21][O:22][CH2:23]Cl)([CH3:19])[CH3:18].[H-].[Na+]>CN(C=O)C>[CH2:14]([O:13][C:11]([C:10]1[C:3]2[C:2]([Cl:1])=[N:7][CH:6]=[N:5][C:4]=2[N:8]([CH2:23][O:22][CH2:21][CH2:20][Si:17]([CH3:19])([CH3:18])[CH3:16])[CH:9]=1)=[O:12])[CH3:15]

Participants

Conditions

Temperature: 0 °C

Procedure

To a stirred mixture of ethyl 4-chloro-7H-pyrrolo[2,3-d]pyrimidine-5-carboxylate (4.00 g, 17.7 mmol) and SEMCl (4.71 mL, 26.6 mmol) in DMF (90 mL) was added sodium hydride (0.851 g, 21.3 mmol) portion-wise at 0° C. The resulting yellow suspension was stirred at 0° C. for one hour and then allowed to warm to room temperature over one hour. The reaction was quenched with water slowly then extracted with ethyl acetate (×3). The combined organic layers were washed with brine (150 mL), dried over sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by chromatography on silica eluting with 0-50% ethyl acetatehexane to afford ethyl-4-chloro-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidine-5-carboxylate. LRMS (ESI) calc'd for C15H23ClN3O3Si [M+H]+: 356; found 356.

Workup

temperatureto warm to room temperature over one hour
customThe reaction was quenched with water slowly
extractionextracted with ethyl acetate (×3)
washThe combined organic layers were washed with brine (150 mL)
dry with materialdried over sodium sulfate
filtrationfiltered
concentrationconcentrated under reduced pressure
customThe residue was purified by chromatography on silica eluting with 0-50% ethyl acetatehexane

Sources & evidence

ORD record: ord-9938c19915ec41849fb1bcff487228b6
Source dataset: uspto-grants-2015_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08993756B2

Reaction notes

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