Thionyl Chloride → 4-Chloro-7H-pyrrolo(2,3-d)pyrimidine-5-carbonitrile

To a suspension of 4-chloro-7H-pyrrolo[2,3-d]pyrimidine-5-carbaldehyde oxime (865 mg, 4.40 mmol, 1.0 eq) in DCM (20 mL), thionyl chloride (3.1 mL, 43.7 mmol, 10.0 eq) was added and the resulting mixture was stirred at RT overnight. The reaction mixture was concentrated in vacuo. The residue was suspended in water (60 mL) and saturated aqueous NaHCO3 was added to adjust the pH to 4. The solid was collected by filtration, rinsed with water followed by ethyl acetate to afford the first batch of product. The filtrate was then extracted with ethyl acetate (50 mL×3). The combined organic layer was washed with brine, dried over Na2SO4 and filtered. The filtrate was concentrated in vacuo and the residue was combined with the above-obtained solid. The crude product was then re-crystallized in ethyl acetate/hexanes (1:1) and dried in vacuo to afford 4-chloro-7H-pyrrolo[2,3-d]pyrimidine-5-carbonitrile (763 mg, 97% yield). ESI-MS m/z: 178.8 [M+H]+, 176.8 [M−H]−.

1. additionwas added
2. concentrationThe reaction mixture was concentrated in vacuo
3. additionsaturated aqueous NaHCO3 was added
4. filtrationThe solid was collected by filtration
5. washrinsed with water
6. customto afford the first batch of product
7. extractionThe filtrate was then extracted with ethyl acetate (50 mL×3)
8. washThe combined organic layer was washed with brine
9. dry with materialdried over Na2SO4
10. filtrationfiltered
11. concentrationThe filtrate was concentrated in vacuo
12. customThe crude product was then re-crystallized in ethyl acetate/hexanes (1:1)
13. customdried in vacuo

ORD record

ord-189c78c7fe614f1ba5dc618b0182e9f5

Source dataset

uspto-grants-2015_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08969363B2