4-Chloro-7H-pyrrolo[2,3-d]pyrimidine, CAS No. 3680-69-1, is a fundamental pharmaceutical intermediate. It can be used in several tyrosine kinase inhibitor (-tinib) drug synthesis as a building block. For instance, other than Tofacitinib, a JAK inhibitor used to treat rheumatic conditions, it can also be ultilized in the synthesis of a new kinase inhibitor Ritlecitinib (PF-06651600) developed by Pfizer. 

To show you the extensive utilization of 4-Chloro-7H-pyrrolo[2,3-d]pyrimidine in the tinib drug development, structures of already approved tinib drugs targeting JAKs (Ruxolitinib, Tofacitinib, Baricitinib, and Abrocitinib) are shown below.

The molecular structure of Ruxolitinib, approved in 2011 for the treatment of various types of myelofibrosis, polycythemia vera in patients who have not responded to or cannot tolerate hydroxyurea, and to treat graft-versus-host disease in cases that are refractory to steroid treatment.

The molecular structure of Tofacitinib, approved in 2012 to treat rheumatic conditions.

The molecular structure of Baricitinib, approved in 2018 for the treatment of moderate to severe rheumatoid arthritis that has responded poorly to at least one TNF antagonist.

The molecular structure of Abrocitinib, approved in 2022 to treat moderate-to-severe atopic dermatitis in adults.

References

https://go.drugbank.com/drugs/DB08877

https://go.drugbank.com/drugs/DB08895

https://go.drugbank.com/drugs/DB11817

https://go.drugbank.com/drugs/DB14973

4-Chloro-7H-pyrrolo[2,3-d]pyrimidine in 2023 FDA approvals

Ritlecitinib (PF-06651600, CAS No. 1792180-81-4) is a highly selective inhibitor of Janus kinase 3 (JAK3) and the tyrosine kinase expressed in hepatocellular carcinoma (TEC) kinase family to treat severe alopecia areata in adults and adolescents 12 years and older.

The molecular structure of Ritlecitinib

The synthetic role of CAS No. 3680-69-1 is shown below, where 4-Chloro-7H-pyrrolo[2,3-d]pyrimidine gives Ritlecitinib the terminal 6 and 5 hetero-rings. 

Reference

https://go.drugbank.com/drugs/DB14924

https://worldwide.espacenet.com/patent/search?q=pn%3DJP2020066629A

https://worldwide.espacenet.com/patent/search/family/074690268/publication/CN112430235A?q=pn%3DCN112430235A

https://pubs.acs.org/doi/10.1021/acs.oprd.9b00198

4-Chloro-7H-pyrrolo[2,3-d]pyrimidine in the future

Other than the already approved drugs, 4-Chloro-7H-pyrrolo[2,3-d]pyrimidine is also seen as the fragment in the new tinib drugs. For example, Delgocitinib, is an investigational for the treatment of moderate to severe chronic hand eczema and is currently in Phase III trials (NCT05355818, NCT06004050) conducted by Leo Pharma. 

The molecular structure of Delgocitinib is shown in the following and the moiety from 4-Chloro-7H-pyrrolo[2,3-d]pyrimidine is highlighted in orange.