Methods of manufacturing of niraparib

A process for preparing an enantiomerically enriched (S)-niraparib tosylate monohydrate of Formula (12), comprising:

• a) contacting a salt of Formula (13) with sodium hydroxide and toluene, to form a compound of Formula (14);
• b) contacting a compound of Formula (15) with sodium azide, ethyl acetate and DMSO, to form a compound of Formula (16);
• c) contacting the compound of Formula (14) with the compound of Formula (16) and TFA, to form a compound of Formula (4);
• d) contacting the compound of Formula (4) with copper(II) trifluoromethanesulfonate (Cu(OTf)2), THF and toluene, to form a compound of Formula (6);
• e) contacting the compound of Formula (6) with lithium hydroxide and ethanol, to form a salt of Formula (8);
• f) contacting the salt of Formula (8) with CDI, TFA, N,N-dimethylformamide (DMF), and ammonium hydroxide, to form a compound of Formula (10);
• g) contacting the compound of Formula (10) with p-Toluenesulfonic acid monohydrate (pTsOH·H2O) and THF, to form (S)-niraparib tosylate monohydrate of Formula (12) as a mixture comprising (R)-niraparib tosylate monohydrate;
• h) contacting the mixture comprising (R)-niraparib tosylate monohydrate and (S)-niraparib tosylate monohydrate with water and a first organic solvent;
• i) separating (S)-niraparib tosylate monohydrate from the mixture by filtration to form an enantiomerically enriched (S)-niraparib tosylate monohydrate;
• and
• j) contacting the enantiomerically enriched (S)-niraparib tosylate monohydrate with a second organic solvent, water, or any combination thereof to form a crystalline form of the enantiomerically enriched (S)-niraparib tosylate monohydrate.