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 (E-4) (865 mg, 4.40 mmol, 1.0 eq) in DCM (20 mL), thionyl chloride (3.1 mL, 43.7 mmol, 10.0 eq) is added and the resulting mixture is stirred at RT overnight. The reaction mixture is concentrated in vacuo. The residue is suspended in water (60 mL) and saturated aqueous NaHCO3 is added to adjust the pH to 4. The solid is collected by filtration, rinsed with water followed by ethyl acetate to afford a first portion of product. The filtrate is then extracted with ethyl acetate (50 mL×3). The combined organic layers are washed with brine, dried over Na2SO4 and filtered. The filtrate is concentrated in vacuo and the residue is combined with the first portion of product. The product is then re-crystallized in ethyl acetate/hexanes (1:1) and dried in vacuo to afford the final product, 4-chloro-7H-pyrrolo[2,3-d]pyrimidine-5-carbonitrile (E-5) as a pale solid.

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

ORD record

ord-ffcaf3d092f44f64bbeb39c130824102

Source dataset

uspto-grants-2015_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09181221B2