Process for producing 4,5-dihydro-1H-pyrazoles and intermediates
AssigneeNovo Nordisk A/S
InventorsJeremy Green, Stefan Mix, Vincent Brunet, Gareth Brown, Drazen Pavlovic
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Abstract
Described are processes for the manufacture of compounds containing a (S)-4,5-dihydro-1H-pyrazole ring. These processes include a chiral resolution step of an intermediate using selected chiral resolving agents. For example, the chiral resolving agents may be selected from (−)-quinine, (R)-phenethylamine, (S)-phenethylamine, (S)-1-naphthylethylamine, (R)-(−)-2-amino-3-methyl-1-butanol, (−)-cinchonidine, (−)-spartein, (R)-1-naphthylethylamine, D-arginine, L-lysine, (S)-(+)-2-pyrrolidinemethanol and (1R,2S)-(+)-cis-1-amino-2-indanol.
Claims28
A process for preparing an enantiomerically enriched compound, comprising the steps of:
- (a) providing a compound of Formula I(a) or I(b) or a tautomer thereof:
- wherein said compound of Formula I(a) or I(b) comprises a mixture of R and S isomers at the (*) carbon atom (C*) and wherein the fourth atom attached to C* is hydrogen or an isotope thereof;
- (b) dissolving the compound of Formula I(a) or I(b) in a solvent to obtain a solution;
- (c) dissolving a chiral resolving agent selected from (−)-quinine, (R)-phenethylamine, (S)-phenethylamine, (S)-1-naphthylethylamine, (R)-(−)-2-amino-3-methyl-1-butanol, (−)-cinchonidine, (−)-spartein, (R)-1-naphthylethylamine, D-arginine, L-lysine, (S)-(+)-2-pyrrolidinemethanol, and (1R,2S)-(+)-cis-1-amino-2-indanol in the solution to form a precipitate and a supernatant;
- and
- (d) separating the precipitate from the supernatant, wherein one of the precipitate or the supernatant comprises the enantiomerically enriched compound comprising a higher concentration in S-enantiomer compared to the R-enantiomer of the compound of Formula I(a) or I(b);
- wherein steps (b) and (c) are carried out simultaneously or sequentially.
Dependencies are inferred from the claim text.