Process for the preparation of tucatinib
AssigneeDr. Reddy's Laboratories, Inc.
InventorsRajeev Rehani BUDHDEV, Sekhar NARIYAM MUNASWAMY, Pradip Kumar SAMANTA, Sridhar VASAM, Subbarao CHIKKAM
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Abstract
The present application relates to process for the preparation of Tucatinib. The present application also relates to the process for the preparation of Tucatinib intermediates. The present application also provides a process for the preparation of amorphous tucatinib. The present application also provides tucatinib triflate salt characterized by PXRD peaks.
Claims15
A one-pot process for the preparation of Tucatinib intermediate of Formula (VI) comprising:
- (a) reacting a compound of Formula (III) with a suitable halogenating reagent to give a compound of Formula (IV);
- wherein X is Cl, Br, and I;
- (b) coupling a compound of Formula (IV) with a compound of Formula (V) in acidic medium to produce a compound of Formula (VI)
- wherein X is defined above.
A process for the preparation of tucatinib intermediate of Formula (VII) comprising transfer hydrogenation of compound of Formula (VI) to provide a compound of Formula (VII)
A process for the preparation of amorphous Tucatinib (I), comprising
- a) coupling a compound of Formula (VII) with compound of Formula (VIII) or an acid-addition salt thereof in presence of an organic base to produce tucatinib Formula (I) or an acid-addition salt thereof;
- and
- b) optionally, treating the acid-addition salt of compound of formula (I) with a base in a suitable solvent.
A process for preparing amorphous tucatinib, comprising use of crystalline form of Tucatinib triflate of formula (IX),
- which is characterized by:
- (i) Powder X-ray diffactogram having peaks at about 6.9, 8.5, 10.6, 13.9, 18.4, 21.3, 25.4±0.2 °2θ;
- (ii) DSC thermogram as shown in FIG. 2.
Dependencies are inferred from the claim text.