The colony-stimulating factor 1 receptor (CSF1R) is a protein kinase emerging as an attractive target with clinical relevance in cancer, CNS and inflammatory diseases. Molecular docking experiments followed by synthesis and structure-activity relationship have been used to identify low molecular weight structures as promising hits for lead optimization. These molecules are synthesized from a 4-chloro-6-iodo-pyrrolo[2,3-d]pyrimidine building block using Negishi and Suzuki-Miyaura cross-coupling reactions in high yields. Several inhibitors possessed excellent enzymatic potency, and the parent compound preferably binds to the autoinhibited form of CSF1R. Cellular and in vivo profiling indicate that further tuning of drug structure is needed prior to efficacy studies.