We claim:
1. A process for the preparation of (lR,2S,5S)-N-{(lS)-l-Cyano-2-[(3S)-2-oxo pyrrolidin-3-yl]ethyl}-6,6-dimethyl-3-[3-methyl-N-(trifluoroacetyl)-L-valyl]-3-azabicyclo[3,1.0]hexane-2-carboxamide (Nirmatrelvir) having process impurities less than 0.15%, which comprises:
a) dissolving (1 R,2S,5S)-N-{(IS)-1-Cyano-2-[(3S)-2-oxopyrrolidin-3-yl]ethyl}-6,6-dimethyl-3-[3-methyl-N-(trifluoroacetyl)-L-valyl]-3-azabicyclo[3.I.O]hexane-2-carboxamide in alcohol ;
b) heating the obtained reaction mass to 50-70°C
c) cooling the obtained reaction mass to 0-20°C;
d) isolating the (]R,2S,5S)-N-{(lS)-l-Cyano-2-[(3S)-2-oxopyrrolidin-3-yl]ethyl}-6,6-dimethyl-3-[3-methyl-N-(trifluoroacetyl)-L-valyl]-3-azabicyclo[3.1.Ojhexane-2-carboxamide alcohol solvate in crystalline form; and .
e) isolating the (1R52S,5S)-N-{(lS)-l-Cyano-2-[(3S)-2-oxopyrrolidin-3-yl]ethyl}-6,6-dimethyl-3-[3-methyl-N-(trifluoroacetyl)-L-valyl]-3-azabicyclo[3.l.0]hexane-2-carboxamide by desolvating the alcohol solvate of step (d).
Wherein alcohol is Isopropyl alcohol.
2. The process as claimed in claim 1, wherein desolvation of alcohol crystalline solvate of (lR;2S,5S)-N-{(!S)-l-Cyano-2-[(3S)-2-oxopyrrolidin-3-yl]ethyl}-6,6-dimethyl-3-[3-methyl-N-(trifluoroacetyl)-L-valyl]-3-azabicyclo[3.1.0]hexane-2-carboxamide is carried out by way of solvent-anti solvent technique, evaporation of solvent and hot melting.
3. A process for the preparation of alcohol solvate of (IR,2S,5S)-N-{(IS)-l-Cyano-2-[(3S)-2-oxopyrrolidin-3-yl]ethyl}-6,6-dimethyl-3-[3-inethyl-N-(trifluoroacetyl)-L-va1yl]-3-azabicyclo[3.1,0]hexane-2-carboxamide, which comprises:
a) dissolving (lR,2S,5S)-N-{(lS)-l-Cyano-2-[(3S)-2-oxopyrrolidin-3-yl]ethyl}-6,6-dimethyl-3-[3-methyl-N-(trifluoroacetyl)-L-valyl]-3-azabicyclo[3.l.0]hexane-2-carboxamide in alcohol;
b) heating the obtained reaction mass to 50-70°C;
c) cooling the obtained reaction mass to 0-20°C; and
d) isolating the (IR,2S,5S)-N-{(IS)-l-Cyano-2-[(3S)-2-oxopyrrolidin-3-yl]ethyl}-6,6-dimethyl-3-[3-methyl-N-(trifluoroacetyl)-L-va]yl]-3-azabicyclo[3.l.0]hexane-2-carboxamide alcohol solvate in crystalline form. Wherein alcohol is selected from the group comprising of Ci-e alcohols.
4. The process as claimed in claim l,an isopropanol solvate of (lR,2S,5S)-N-{(IS)-l-Cyano-2-[(3S)-2-oxopyrrolidin-3-yl]ethyl}-6,6-dimethyl-3-[3-methyl-N-(trifluoroacetyl)-L-valyl]-3-azabicydo[3.l.0]hexane-2-carboxamide having the X-ray powder diffraction pattern shown in Figure 1 and having peaks at 7.4 and 8.8±0.2°6 and designated as Form H I.
5. The process as claimed in claim l,an isopropanol solvate of (1R,2S,5S)-N-{(1 S)-l-Cyano-2-[(3S)-2-oxopyrrolidin-3-yl]ethyl}-6,6-dimethyl-3-[3-methyl-N-(trifluoroacetyl)-L-valyl]-3-azabicyclo[3.1.0]hexane-2-carboxamide having DSC is as shown in Figure 2, with peak at ~I25.4°C.
6. Use of crystalline alcohol solvate form of (]R,2S,5S)-N-{(IS)-l-Cyano-2-[(3S)-2-oxopyrrolidin-3-yl]ethyl}-6,6-dimethyl-3-[3-methyl-N-(trifluoroacetyl)-L-valyl]-3-azabicyclo[3.1.0]hexane-2-carboxamide in the preparation of (1 R52S55S)-N-{( IS)-1 -Cyano-2-[(3S)-2-oxopyrrolidin-3-yl]ethyl }-6,6-dimethyl-3-[3-methyl-N-(trifluoroacetyl)-L-valyl]-3-azabicyc!o[3.1.0]hexane-2-carboxamide.