Process for preparation of apalutamide
The present invention relates to a process for the preparation of apalutamide. In particular, the present invention relates to a process for the preparation of apalutamide and its intermediates. The present invention also relates to pharmaceutical compositions comprising apalutamide.
1. A process the preparation of apalutamide of Formula (I)
the process comprising:
reacting a compound of Formula (II′), or salts thereof,
wherein R is hydrogen,
with a compound of Formula (III),
optionally in the presence of an alcohol or phenol to obtain apalutamide of Formula (I).
2. The process according to claim 1 , wherein the compound of Formula (II′) is prepared by a process comprising reacting a compound of Formula (IV) with a compound of Formula (V); and
optionally, converting compound of Formula (II′) to salts thereof,
wherein, R 1 and R 2 are either a leaving group or amine and interchangeable, with a proviso that both R 1 and R 2 are not same, and wherein the leaving group is selected from the group consisting of F, Cl, Br, I, OTs, OTf and OMs.
3. The process according to claim 1 , wherein the salt of compound of Formula (II′) is triethylamonium salt.
4. A compound of Formula (IIs),
5. The compound according to claim 4 , is crystalline.
6. The compound according to claim 5 , wherein the crystalline compound of Formula (IIs) is characterized by X-ray powder diffraction (XRD) having peaks expressed in degrees 2θ (±0.2° 2θ) at about 6.7°, 12.0°, and 13.5°.
7. The process according to claim 1 , wherein the compound of Formula (III) is crystalline.
8. The process according to claim 7 wherein the crystalline compound of Formula (III) is characterized by X-ray powder diffraction (XRD) having peaks expressed in degrees 2θ (±0.2° 2θ) at about 15.1°, 17.7°, 19.9°, and 20.9°.
9. A process for the preparation of apalutamide, the process comprising
reacting a compound of Formula (IIs)
with a compound of Formula(III),
optionally in the presence of alcohol or phenol or mixture thereof to obtain apalutamide of Formula (I).
10. A substantially pure apalutamide having a purity of about 99.8% or more, by area percentage of HPLC.
11. The substantially pure apalutamide according to claim 10 having diketo-impurity-A of 0.10% or less, by area percentage of HPLC.