US 9,809,549 B2
Malate salt of N-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}phenyl)-N′(4-fluorophenyl)cyclopropane-1,1-dicarboxamide, and crystalline forms therof for the treatment of cancer
Adrian St. Clair Brown, Ely (GB); Peter Lamb, Oakland, CA (US); and William P. Gallagher, Princeton, NJ (US)
Assigned to Exelixis, Inc., South San Francisco, CA (US)
Filed by Exelixis, Inc., South San Francisco, CA (US)
Filed on Jul. 25, 2014, as Appl. No. 14/340,871.
Application 14/340,871 is a division of application No. 13/145,054, granted, now 8,877,776, previously published as PCT/US2010/021194, filed on Jan. 15, 2010.
Claims priority of provisional application 61/145,421, filed on Jan. 16, 2009.
Prior Publication US 2015/0057310 A1, Feb. 26, 2015
Int. Cl. C07D 215/22 (2006.01); C07D 215/233 (2006.01)
CPC C07D 215/22 (2013.01) [C07D 215/233 (2013.01)] 5 Claims
1. N-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}phenyl)-N′-(4-fluorophenyl) cyclopropane-1,1-dicarboxamide (L) malate salt, wherein said salt is in crystalline Form N-1 and said Form N-1 is characterized by at least one of the following:
(i) a solid state 13C NMR spectrum with four or more peaks selected from 18.1, 42.9, 44.5, 70.4, 123.2, 156.2, 170.8, 175.7, and 182.1, ±0.2 ppm;
(ii) a powder x-ray diffraction pattern (CuKα λ=1.5418 Å) comprising four or more 2θ values selected from: 12.8±0.2° 2θ, 13.5±0.2° 2θ, 16.9±0.2° 2θ, 19.4±0.2° 2θ, 21.5±0.2° 2θ, 22.8±0.2° 2θ, 25.1±0.2° 2θ, 27.6±0.2° 2θ, wherein measurement of the crystalline form is at room temperature; and/or
(iii) an x-ray powder diffraction (XRPD) pattern substantially in accordance with the pattern shown in FIG. 1.