C5aR antagonists
Compounds are provided that are modulators of the C5a receptor. The compounds are substituted piperidines and are useful in pharmaceutical compositions, methods for the treatment of diseases and disorders involving the pathologic activation of C5a receptors.
1. A process for preparing a compound of formula (ii),
comprising
(a) treating a compound of formula (i)
with H 2 and a platinum oxide catalyst under reducing conditions; and
(b) subjecting the product of step (a) to resolution with di-toluoyl-L-tartaric acid to provide compound (ii).
2. A process in accordance with claim 1 , wherein compound (ii) is prepared in about 97% enantiomeric excess.
3. A process in accordance with claim 1 , further comprising a step wherein the compound of formula (i) is prepared by treating ethyl 2-chloronicotinate with N-Boc-4-aminophenylboronic acid in the presence of Pd(PPh 3 ) 4 .
4. A process in accordance with claim 1 , wherein step (a) is carried out in ethanol and HCl.
5. A process in accordance with claim 1 , wherein step (b) is carried out in THF and tert-butyl methyl ether.
6. A process for preparing a compound of formula (ii),
comprising subjecting a compound of formula (iia)
to resolution with di-toluoyl-L-tartaric acid to provide compound (ii).
7. A process in accordance with claim 6 , wherein compound (ii) is prepared in about 97% enantiomeric excess.
8. A compound having the formula:
9. A compound of claim 8 , having the formula:
which is provided in about 97% enantiomeric excess.
10. A compound having the formula: