دورية أكاديمية
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Modular, automated synthesis of spirocyclic tetrahydronaphthyridines from primary alkylamines.

التفاصيل البيبلوغرافية
العنوان: Modular, automated synthesis of spirocyclic tetrahydronaphthyridines from primary alkylamines.
المؤلفون: Cao Q; Department of Chemistry, University of Bath, Claverton Down, Bath, BA2 7AY, UK., Tibbetts JD; Department of Chemistry, University of Bath, Claverton Down, Bath, BA2 7AY, UK., Wrigley GL; Medicinal Chemistry, Oncology R&D, AstraZeneca, Cambridge, CB4 0WG, UK., Smalley AP; UCB, 216 Bath Road, Slough, SL1 3WE, UK., Cresswell AJ; Department of Chemistry, University of Bath, Claverton Down, Bath, BA2 7AY, UK. a.j.cresswell@bath.ac.uk.
المصدر: Communications chemistry [Commun Chem] 2023 Oct 04; Vol. 6 (1), pp. 215. Date of Electronic Publication: 2023 Oct 04.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Springer Nature Country of Publication: England NLM ID: 101725670 Publication Model: Electronic Cited Medium: Internet ISSN: 2399-3669 (Electronic) Linking ISSN: 23993669 NLM ISO Abbreviation: Commun Chem Subsets: PubMed not MEDLINE
أسماء مطبوعة: Original Publication: [London] : Springer Nature, [2018]-
مستخلص: Spirocyclic tetrahydronaphthyridines (THNs) are valuable scaffolds for drug discovery campaigns, but access to this 3D chemical space is hampered by a lack of modular and scalable synthetic methods. We hereby report an automated, continuous flow synthesis of α-alkylated and spirocyclic 1,2,3,4-tetrahydro-1,8-naphthyridines ("1,8-THNs"), in addition to their regioisomeric 1,6-THN analogues, from abundant primary amine feedstocks. An annulative disconnection approach based on photoredox-catalysed hydroaminoalkylation (HAA) of halogenated vinylpyridines is sequenced in combination with intramolecular S N Ar N-arylation. To access the remaining 1,7- and 1,5-THN isomers, a photoredox-catalysed HAA step is telescoped with a palladium-catalysed C-N bond formation. Altogether, this provides a highly modular access to four isomeric THN cores from a common set of unprotected primary amine starting materials, using the same bond disconnections. The simplifying power of the methodology is illustrated by a concise synthesis of the spirocyclic THN core of Pfizer's MC4R antagonist PF-07258669.
(© 2023. Springer Nature Limited.)
References: ACS Med Chem Lett. 2021 Dec 08;13(1):84-91. (PMID: 35059127)
Angew Chem Int Ed Engl. 2020 Aug 24;59(35):14986-14991. (PMID: 32391968)
Angew Chem Int Ed Engl. 2016 Oct 24;55(44):13650-13657. (PMID: 27573303)
J Med Chem. 2020 Nov 12;63(21):12542-12573. (PMID: 32930584)
Org Biomol Chem. 2013 Feb 28;11(8):1358-66. (PMID: 23321684)
J Med Chem. 2011 May 26;54(10):3451-79. (PMID: 21504168)
J Med Chem. 2022 Jul 14;65(13):8699-8712. (PMID: 35730680)
Org Lett. 2015 Aug 21;17(16):4054-7. (PMID: 26250901)
Bioorg Med Chem Lett. 2004 Sep 6;14(17):4515-8. (PMID: 15357983)
J Am Chem Soc. 2007 Aug 22;129(33):10211-9. (PMID: 17655300)
Angew Chem Int Ed Engl. 2012 Jan 27;51(5):1114-22. (PMID: 22271624)
J Am Chem Soc. 2016 Nov 9;138(44):14554-14557. (PMID: 27786439)
J Med Chem. 2019 Jul 25;62(14):6422-6468. (PMID: 30794752)
Chem Rev. 2020 Mar 11;120(5):2613-2692. (PMID: 32064858)
Angew Chem Int Ed Engl. 2013 Dec 2;52(49):12915-9. (PMID: 24222178)
Org Biomol Chem. 2016 Jul 12;14(28):6683-6. (PMID: 27334098)
J Org Chem. 2012 Oct 5;77(19):8518-26. (PMID: 22950872)
J Med Chem. 2021 Jan 14;64(1):150-183. (PMID: 33381970)
Org Biomol Chem. 2016 Feb 7;14(5):1599-610. (PMID: 26741115)
J Am Chem Soc. 2022 Jul 6;144(26):11459-11481. (PMID: 35731810)
J Med Chem. 2017 May 11;60(9):3552-3579. (PMID: 28177632)
Bioorg Med Chem. 2010 Jun 15;18(12):4351-62. (PMID: 20483621)
Org Lett. 2016 Jun 3;18(11):2730-3. (PMID: 27200456)
J Am Chem Soc. 2021 Oct 6;143(39):15936-15945. (PMID: 34543004)
ACS Med Chem Lett. 2016 Oct 17;7(12):1173-1178. (PMID: 27994759)
J Med Chem. 2014 Dec 26;57(24):10257-74. (PMID: 25255204)
J Org Chem. 2004 Mar 19;69(6):1959-66. (PMID: 15058940)
J Org Chem. 2004 Dec 10;69(25):8723-30. (PMID: 15575749)
Chemistry. 2018 Jul 20;24(41):10443-10451. (PMID: 29732638)
J Org Chem. 2004 Oct 15;69(21):7171-82. (PMID: 15471466)
Org Lett. 2017 Sep 15;19(18):4770-4773. (PMID: 28857570)
Angew Chem Int Ed Engl. 2003 Sep 22;42(36):4370-3. (PMID: 14502714)
J Am Chem Soc. 2021 Oct 6;143(39):15946-15959. (PMID: 34551248)
Chem Rev. 2022 Jan 26;122(2):2752-2906. (PMID: 34375082)
J Med Chem. 2018 Sep 27;61(18):8417-8443. (PMID: 30215258)
J Med Chem. 2023 Mar 9;66(5):3195-3211. (PMID: 36802610)
Nat Rev Drug Discov. 2022 Jan;21(1):60-78. (PMID: 34535788)
J Med Chem. 2020 Jul 9;63(13):6624-6647. (PMID: 32049517)
Angew Chem Int Ed Engl. 2016 Sep 26;55(40):12479-83. (PMID: 27596095)
Org Lett. 2020 Oct 16;22(20):7964-7970. (PMID: 32970449)
Org Lett. 2007 Feb 1;9(3):393-6. (PMID: 17249770)
Chemistry. 2020 Dec 18;26(71):16952-16974. (PMID: 32427387)
Org Lett. 2016 Apr 15;18(8):1713-5. (PMID: 27026179)
معلومات مُعتمدة: EP/X026566/1 RCUK | Engineering and Physical Sciences Research Council (EPSRC); UF150533 Royal Society
تواريخ الأحداث: Date Created: 20231004 Latest Revision: 20231119
رمز التحديث: 20231119
مُعرف محوري في PubMed: PMC10550966
DOI: 10.1038/s42004-023-01012-2
PMID: 37794068
قاعدة البيانات: MEDLINE
الوصف
تدمد:2399-3669
DOI:10.1038/s42004-023-01012-2