{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,28]],"date-time":"2026-06-28T19:20:25Z","timestamp":1782674425223,"version":"3.54.5"},"reference-count":34,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2024,10,7]],"date-time":"2024-10-07T00:00:00Z","timestamp":1728259200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005416","name":"Research Council of Norway","doi-asserted-by":"publisher","award":["NFR 284937"],"award-info":[{"award-number":["NFR 284937"]}],"id":[{"id":"10.13039\/501100005416","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005416","name":"Research Council of Norway","doi-asserted-by":"publisher","award":["226244\/F50"],"award-info":[{"award-number":["226244\/F50"]}],"id":[{"id":"10.13039\/501100005416","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Norwegian NMR Platform","award":["NFR 284937"],"award-info":[{"award-number":["NFR 284937"]}]},{"name":"Norwegian NMR Platform","award":["226244\/F50"],"award-info":[{"award-number":["226244\/F50"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>7-Azaindoles are compounds of considerable medicinal interest. During development of the structure\u2013activity relationship for inhibitors of the colony stimulated factor 1 receptor tyrosine kinase (CSF1R), a specific 2-aryl-1H-pyrrolo[2,3-b]pyridin-4-amine was needed. Two different synthetic strategies were evaluated, in which the order of the key C-C and C-N cross-coupling steps differed. The best route relied on a chemoselective Suzuki\u2013Miyaura cross-coupling at C-2 on a 2-iodo-4-chloropyrrolopyridine intermediate, and subsequently a Buchwald\u2013Hartwig amination with a secondary amine at C-4. Masking of hydroxyl and pyrroles proved essential to succeed with the latter transformation. The final trimethylsilylethoxymethyl (SEM) deprotection step was challenging, as release of formaldehyde gave rise to different side products, most interestingly a tricyclic eight-membered 7-azaindole. The target 2-aryl-1H-pyrrolo[2,3-b]pyridin-4-amine (compound 3c) proved to be 20-fold less potent than the reference inhibitor, confirming the importance of the N-3 in the pyrrolopyrimidine parent compound for efficient CSF1R inhibition.<\/jats:p>","DOI":"10.3390\/molecules29194743","type":"journal-article","created":{"date-parts":[[2024,10,8]],"date-time":"2024-10-08T04:29:26Z","timestamp":1728361766000},"page":"4743","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Synthetic Routes to 2-aryl-1H-pyrrolo[2,3-b]pyridin-4-amines: Cross-Coupling and Challenges in SEM-Deprotection"],"prefix":"10.3390","volume":"29","author":[{"given":"Srinivas Reddy","family":"Merugu","sequence":"first","affiliation":[{"name":"Department of Chemistry, Norwegian University of Science and Technology (NTNU), N-7491 Trondheim, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sigrid","family":"Selmer-Olsen","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Norwegian University of Science and Technology (NTNU), N-7491 Trondheim, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camilla Johansen","family":"Kaada","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Norwegian University of Science and Technology (NTNU), N-7491 Trondheim, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eirik","family":"Sundby","sequence":"additional","affiliation":[{"name":"Department of Materials Science and Engineering, Norwegian University of Science and Technology (NTNU), N-7491 Trondheim, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B\u00e5rd Helge","family":"Hoff","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Norwegian University of Science and Technology (NTNU), N-7491 Trondheim, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,10,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2758","DOI":"10.1021\/jp9630232","article-title":"Photophysics and Biological Applications of 7-Azaindole and Its Analogs","volume":"101","author":"Smirnov","year":"1997","journal-title":"J. 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