Reactions of 1,4-Benzodiazepinic N-Nitrosoamidines with Tosylmethyl Isocyanide: A Novel Synthesis of Midazolam

Carlos del Pozo; Alberto Macías; Eduardo Alonso; Javier González

doi:10.1055/s-2004-831243

RSS-Feed abonnieren

Bitte kopieren Sie die angezeigte URL und fügen sie dann in Ihren RSS-Reader ein.

https://www.thieme-connect.de/rss/thieme/de/10.1055-s-00000084.xml

Teilen / Bookmarken

Facebook X Linkedin Weibo

PDF herunterladen

Synthesis 2004(16): 2697-2703
DOI: 10.1055/s-2004-831243

PAPER

Reactions of 1,4-Benzodiazepinic N-Nitrosoamidines with Tosylmethyl Isocyanide: A Novel Synthesis of Midazolam

Carlos del Pozo*, Alberto Macías, Eduardo Alonso, Javier González*
Departamento de Química Orgánica e Inorgánica, Universidad de Oviedo, Julián Clavería 8, 33071 Oviedo, Spain
e-Mail: fjgf@uniovi.es;

Weitere Informationen

Publikationsverlauf

Received 14 April 2004
Publikationsdatum:
22. September 2004 (online)

Abstract
Volltext
Referenzen

Lizenzen und Reprints Alle Artikel dieser Rubrik

Abstract

Reaction of 1,4-benzodiazepinic N-nitrosoamidines, used as synthetic equivalents of imidoyl chlorides, with the mono-anion of tosylmethyl isocyanide is described. The process gives entry to 3-(4-tosyl)imidazo[1,5-a][1,4]benzodiazepines, compounds which have not been described yet in the literature. These systems can be derivatized to the corresponding trisubstituted 1,4-benzodiazepines by alkylation or acylation of the imidazole ring. These new heterocyclic derivatives are potentially useful in the field of medicinal chemistry. In addition, midazolam 3, the anesthetic properties of which are well established, can be easily prepared in one step by desulfonylation of compound 7a.

Key words

heterocycles - cyclizations - reductions - benzodiazepines - isocyanides

References.

40-1a Benzodiazepines Divided: A Multidisciplinary Review Wiley; New York: 1983.

Google Scholar
40-1b Bock MG. DiPardo RM. Evans BE. Rittle KE. Whitter WL. Veber DF. Anderson PS. Freidinger RM. J. Med. Chem. 1989, 32: 13

Google Scholar
40-2 Sneader W. In Comprehensive Medicinal Chemistry Vol. 1: Hansch C. Sammes PG. Taylor JB. Pergamon; London: 1990. p.65

Google Scholar
40-3a Archer GA. Sternbach LH. Chem. Rev. 1968, 68: 747

Google Scholar
40-3b Sharp JT. In Comprehensive Heterocyclic Chemistry II Vol 7: Katritzky AR. Rees CW. Pergamon; Amsterdam: 1984. p.593

Google Scholar
40-3c Tucker H. Le Count DJ. In Comprehensive Heterocyclic Chemistry II Vol 9: Katritzky AR. Rees CW. Scriven EFV. Elsevier; Amsterdam: 1996. p.151

Google Scholar
For 1,4-benzodizazepines as inhibitors of reverse transcriptase, see:
40-4a Robl JA. Cimarusti MP. Simpkins LM. Brown B. Ryono DE. Bird JE. Asaad MM. Schaeffer TR. Trippodo NC. J. Med. Chem. 1996, 39: 494

Google Scholar
40-4b Merluzzi VJ. Hargrave KD. Labadia M. Grozinger K. Skoog M. Wu JC. Shih C.-K. Eckner K. Hattox S. Adams J. Rosenthal AS. Faanes R. Eckner RJ. Koup RA. Sullivan JL. Science 1990, 250: 1411

Google Scholar
For 1,4-benzodiazepines as antitumor and gene targeted drugs, see:
40-5a Wang T. Lui AS. Cloudsdale IS. Org. Lett. 1999, 1: 1835

Google Scholar
40-5b Novelli F. Sparatore A. Tasso B. Sparatore F. Bioorg. Med. Chem. Lett. 1999, 9: 3031

Google Scholar
40-5c Wilson SC. Howard PW. Forrow SM. Hartley JA. Adams LJ. Jenkins TC. Kelland LR. Thurston DE. J. Med. Chem. 1999, 42: 4028

Google Scholar
40-6 For 1,4-benzodiazepines as inhibitors of phosphodiesterases PDE4, see: Pascal Y. Andrianjara CR. Auclair E. Avenel N. Bertin B. Calvet A. Féru F. Lardon S. Moodley I. Ouagued M. Payne A. Pruniaux M.-P. Szilagyi C. Bioorg. Med. Chem. Lett. 2000, 10: 35

Google Scholar
For 1,4-benzodiazepines as potent and selective oxytocin antagonist, see:
40-7a Evans B. Pipe A. Clark L. Banks M. Bioorg. Med. Chem. Lett. 2001, 11: 1297

Google Scholar
40-7b Wyatt PG. Allen MJ. Chilcott J. Hickin G. Miller ND. Woollard PM. Bioorg. Med. Chem. Lett. 2001, 11: 1301

Google Scholar
For 1,4-benzodiazepines as antagonists of the GPllb/llla receptor, see:
40-8a Hayes JF. Synlett 1999, 865

Google Scholar
40-8b Andrews IP. Atkins RJ. Badham RF. Bellingham RK. Breen GF. Carey JS. Etridge SK. Hayes JF. Hussain N. Morgan DO. Share AC. Smith SAC. Walsgrove TC. Wells AS. Tetrahedron Lett. 2001, 42: 4915

Google Scholar
40-9 For 1,4-benzodiazepines as cholecystokinin (CCK-A) receptor antagonists, see: Sherrill RG. Berman JM. Birkemo L. Croom DK. Dezube L. Ervin GN. Grizzle MK. James MK. Johnson MF. Queen KL. Rimele TJ. Vanmiddlesworth F. Sugg EE. Bioorg. Med. Chem. Lett. 2001, 11: 1145

Google Scholar
For 1,4-benzodiazepines as herbicides, see:
40-10a Karp GM. Manfredi MC. Guaciaro MA. Ortlip CL. Marc P. Szamosi IT. J. Agric. Food Chem. 1997, 45: 493

Google Scholar
40-10b Karp GM. J. Org. Chem. 1999, 64: 8156

Google Scholar
Google Scholar
40-11a Vida JA. In Medicinal Chemistry Wolf MW. Burger A. Wiley; New York: 1981. p.787

Google Scholar
40-11b Fryer RI. In Comprehensive Heterocyclic Chemistry Vol 3: Hansch C. Pergamon Press; New York: 1990. p.539

Google Scholar
40-12a Hester JB. Rudzik AB. Kamdar BV. J. Med. Chem. 1971, 14: 1078

Google Scholar
40-12b Schulte E. Dtsch. Apoth.-Ztg. 1975, 115: 1243

Google Scholar
40-12c Gilman NW. Holland BC. Fryer RI. J. Heterocycl. Chem. 19 77, 14: 1163

Google Scholar
40-12d Walser A. Benjamin LE. Flynn T. Mason C. Schwartz R. Fryer RI. J. Org. Chem. 1978, 43: 936

Google Scholar
40-13a Hester JB. Duchamp D. Chidester CG. Tetrahedron Lett. 1971, 1609

Google Scholar
40-13b Coffen DL. DeNoble JP. Evans EL. Field GF. Fryer RI. Katonak DA. Mandel BJ. Sternbach LH. Zally WJ. J. Org. Chem. 1974, 39: 167

Google Scholar
40-13c Gall M. Hester JB. Rudzik AD. Lahti RA. J. Med. Chem. 1976, 19: 1057

Google Scholar
40-13d Hester JB. J. Heterocycl. Chem. 1980, 17: 575

Google Scholar
40-13e Hester JB. Rudzik AD. Voigtlander PFV. J. Med. Chem. 1980, 23: 392

Google Scholar
40-13f Hester JB. Rudzik AD. Voigtlander PFV. J. Med. Chem. 1980, 23: 402

Google Scholar
40-13g Hester HB. Rudzik AD. Voigtlander PFV. J. Med. Chem. 1980, 23: 643

Google Scholar
40-13h Gall M. Kamdar BV. J. Med. Chem. 1981, 24: 1575

Google Scholar
40-13i Walser A. Fryer RI. J. Heterocycl. Chem. 1983, 20: 551

Google Scholar
40-13j Gall M. Kamdar BV. J. Heterocycl. Chem. 1988, 25: 1649

Google Scholar
40-13k Banks WL. Digenis GA. Tetrahedron Lett. 1989, 6473

Google Scholar
40-13l Hester JB. Ludens JH. Emmert DE. West BE. J. Med. Chem. 1989, 32: 1157

Google Scholar
40-13m Walser A. Flynn T. Mason C. Crowley H. Maresca C. Yaremko B. O’Donnel M. J. Med. Chem. 1991, 34: 1209

Google Scholar
40-14 Ning RY. Fryer RI. Madan PB. Sluboski BC. J. Org. Chem. 1976, 41: 2724

Google Scholar
40-15 Walser A. Fryer RI. J. Org. Chem. 1975, 40: 153

Google Scholar
40-16 van Leusen AM. Lect. Heterocycl. Chem. 1980, 5: S-111

Google Scholar
40-17a van Nispen SPJM. Mensink C. van Leusen AM. Tetrahedron Lett. 1980, 3723

Google Scholar
40-176b Massa S. Di Santo R. Costi R. Mai A. Artico M. Med. Chem. Res. 1993, 3: 192

Google Scholar
40-17c Di Santo R. Massa S. Artico M. Il Farmaco 1993, 48: 209

Google Scholar
40-17d Sisko J.; J. Org. Chem.; 1998, 63: 4529
40-17e Mendiola J. Minguez JM. Alvarez-Buylla J. Vaquero JJ. Org. Lett. 2000, 2: 3253

Google Scholar
40-17f Sisko J. Kassick AJ. Mellinger M. Filan JJ. Allen A. Olsen MA. J. Org. Chem. 2000, 65: 1516

Google Scholar
40-17g Chen P. Barrish JC. Iwanowicz E. Lin J. Bernarz MS. Chen B.-C. Tetrahedron Lett. 2001, 4293

Google Scholar
40-17h Barret AGM. Cramp SM. Hennessy A. Procopiou PA. Roberts RS. Org. Lett. 2001, 3: 271

Google Scholar
40-17i Kobayashi K. Matsumoto T. Irisawa S. Yoneda K. Morikawa O. Konishi H. Heterocycles 2001, 55: 973

Google Scholar
40-17j Nair V. Vinod AU. Rajesh C. J. Org. Chem. 2001, 66: 4427

Google Scholar
40-18 van Leusen AM. Wildeman J. Oldenziel OH. J. Org. Chem. 1977, 42: 1153

Google Scholar
40-19a Walser A. Fryer RI. Sternbach LM. J. Heterocycl. Chem. 1974, 11: 619

Google Scholar
40-19b Walser A. Benjamin L. Flynn T. Mason C. Schwartz R. Fryer R. J. Org. Chem. 1978, 43: 936

Google Scholar
40-20 Bock MG. Di Pardo RM. Evans BE. Rittle KE. Veber DF. Freidinger RM. Hirshfield J. Springer JP. J. Org. Chem. 1987, 52: 3232

Google Scholar
40-21 Bakhtiar C. Smith EH. J. Chem. Soc., Perkin Trans. 1 1994, 243

Google Scholar
40-22 Nájera C. Yus M. Tetrahedron 1999, 55: 10547

Google Scholar
40-23 Addie MS. Taylor RJV. J. Chem. Soc., Perkin Trans. 1 2000, 527

Google Scholar
40-24a Holton RA. Crouse DJ. Williams AD. Kennedy RM. J. Org. Chem. 1987, 52: 2317

Google Scholar
40-24b Adrio J. Rivero MR. Carretero JC. Angew. Chem. Int. Ed. 2000, 39: 2906

Google Scholar
40-24c Adrio J. Rivero MR. Carretero JC. Chem.-Eur. J. 2001, 7: 2435

Google Scholar

40-25

For a slightly different reduction process using Zn-AcOH and leading to a similar product see earlier reference.^13m