Practical synthesis of 2-(2-isopropylaminothiazol-4-yl)-7-methoxy-1H- quinolin-4-one: Key intermediate for the synthesis of potent HCV NS3 protease inhibitor BILN 2061

Synthesis

Volumn , Issue 15, 2006, Pages 2563-2567

  Frutos, Rogelio P ^a   Haddad, Nizar ^a   Houpis, Ioannis N ^a,c   Johnson, Michael ^b,d   Smith Keenan, Lana L ^a   Fuchs, Victor ^a   Yee, Nathan K ^a   Farina, Vittorio ^a   Faucher, Anne Marie ^b   Brochu, Christian ^b   Haché, Bruno ^b   Duceppe, Jean Simon ^b   Beaulieu, Pierre ^b  

^a BOEHRINGER INGELHEIM PHARMACEUTICALS INC   (United States)

^b BOEHRINGER INGELHEIM CANADA LTD   (Canada)

^c JANSSEN RESEARCH AND DEVELOPMENT   (Belgium)

^d BATTELLE MEMORIAL INSTITUTE   (United States)

Author keywords

BILN2061; Hepatitis C virus; Protease inhibitor; Quinolone; Sugasawa

Indexed keywords

METHANE; REACTION KINETICS; SYNTHESIS (CHEMICAL); VIRUSES;

BILN2061; HEPATITIS C VIRUS; PROTEASE INHIBITOR; QUINOLONE; SUGASAWA;

NITROGEN COMPOUNDS;

2 (2 ISOPROPYLAMINOTHIAZOL 4 YL) 7 METHOXY 1H QUINOLIN 4 ONE; 2 (2 ISOPROPYLAMINOTHIAZOL 4 YL) 7 METHOXY 4A,8A DIHYDRO 1H QUINOLIN 4 ONE; 7 METHOXY 2 (2 AMINO 4 THIAZOLYL)QUINOLINE; CILUPREVIR; PROTEINASE INHIBITOR; QUINOLINE DERIVATIVE; UNCLASSIFIED DRUG;

ARTICLE; DRUG SYNTHESIS;

EID: 33747194747     PISSN: 00397881     EISSN: None     Source Type: Journal    
DOI: 10.1055/s-2006-942472     Document Type: Article

References (29)

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26. The yield was determined by a quantitative HPLC assay.
27. 6): δ = 22.7, 46.3, 55.7, 106.4, 110.6, 116.8, 123.1, 130.1, 131.5, 137.0, 139.6, 160.2, 161.4, 163.9.
28. Up to 50% of 11 was formed when the reaction was carried out at 50 °C. Electrophilic reaction of 2-aminothiazoles at C-5 is well precedented. In this case, it may be promoted by ionization of the C-2 isopropylamino group, although usually strong bases like sodium amide have been employed to obtain deprotonation at such amino groups. See: Heterocyclic Compounds; Weissberger, A.; Taylor, E. C., Eds.; Wiley: New York, 1979.
29. A manuscript describing the complete assembly of BILN 2061 using 3 is in preparation and will be published in due course.