Process and intermediates for preparing macrolactams
AssigneeMerck Sharp & Dohme Corp.
InventorsFeng Xu, Guy Humphrey, Tao Pei, Zhiguo Jake Song, Tao Wang, Laura Artino
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Abstract
The present invention includes compounds useful as intermediates in the preparation of macrolactams, methods for preparing the intermediates, and methods for preparing macrolactams from the intermediates. One use of the methods and intermediates described herein is in the production of macrolactam compounds able to inhibit HCV NS3 protease activity. HCV NS3 inhibitory compounds have therapeutic and research applications.
Claims13
A method of making Compound A or a salt thereof:
- comprising the step of coupling
- or salt thereof, to
- or salt thereof,
- wherein the coupling comprises the use of a coupling reagent and pyridine or a pyridine derivative.
A compound having the structure of Formula I or a salt thereof:
- wherein R1 is a leaving group, or
- provided that if R1 is a leaving group, then R2 is H;
- and if R1 is Structure I, then R2 is H and R3 is OH, or R2 and R3 are joined together as a covalent bond;
- R4 is either C1-6 alkyl or aryl;
- and
- R5 is either a C1-8 alkyl or C3-8 cycloalkyl.
A method of making Compound 18 comprising the steps of:
- wherein any of compounds 14, 15, 16, 21 and 18 may be provided as salts, and compounds 16 and 21 are not isolated.
Compound selected from the group consisting of:
- a) a crystalline form of Compound A characterized by either (i) an X-ray powder diffraction pattern obtained using copper Kα radiation which comprises 2Θ values in degrees of about 20.5, 5.0, and 18.2;
- or (ii) a solid state carbon-13 CPMAS NMR comprising peaks at about 5.14, 6.31, 12.49, 18.35, 26.81, 28.03, 30.33, 31.27, 34.95, 35.99, 38.68, 42.01, 54.93, 56.39, 60.14, 74.20, 107.02, 120.11, 121.60, 129.73, 134.35, 135.95, 142.89, 148.47, 155.37, 157.32, 160.90, 168.32, 172.17, and 175.53 ppm;
- and
- b) a Compound 19 hydrate characterized by either (i) an X-ray powder diffraction pattern obtained using copper Kα radiation which comprises 2Θ values in degrees of about 8.7, 22.2, and 23.5;
- or (ii) a solid state carbon-13 CPMAS NMR comprising peaks at about 174.7, 172.0, 161.4, 156.8, 156.3, 149.5, 142.1, 133.9, 128.2, 121.3, 105.0, 76.9, 60.7, 57.5, 55.1, 53.5, 35.8, 34.7, 33.4, 32.4, 29.5, 27.8, 24.0, and 20.2 ppm.
Dependencies are inferred from the claim text.