US 9,809,545 B2
Factor XIa inhibitors
Anthony Ogawa, New Providence, NJ (US); Scott Edmondson, Clark, NJ (US); Mark Erion, Mountainside, NJ (US); Santhosh Neelamkavil, Edison, NJ (US); Zhuyan Guo, Scotch Plains, NJ (US); Rudrajit Mal, Edison, NJ (US); Jiafang He, South Brunswick, NJ (US); Weiguo Liu, Princeton, NJ (US); and Ellen K. Vande Bunte, Hawthorne, NJ (US)
Assigned to Merck Sharp & Dohme Corp., Rahway, NJ (US)
Appl. No. 14/778,765
Filed by Merck Sharp & Dohme Corp., Rahway, NJ (US)
PCT Filed Mar. 21, 2014, PCT No. PCT/US2014/031388
§ 371(c)(1), (2) Date Sep. 21, 2015,
PCT Pub. No. WO2014/160592, PCT Pub. Date Oct. 2, 2014.
Claims priority of provisional application 61/805,733, filed on Mar. 27, 2013.
Prior Publication US 2016/0046581 A1, Feb. 18, 2016
Int. Cl. C07D 401/14 (2006.01); C07D 213/64 (2006.01); A61K 31/551 (2006.01); C07D 401/04 (2006.01); C07D 405/14 (2006.01); C07D 413/14 (2006.01); C07D 401/06 (2006.01); C07D 401/10 (2006.01); C07D 401/12 (2006.01); C07D 405/12 (2006.01); C07D 413/06 (2006.01); C07D 413/12 (2006.01); C07D 471/04 (2006.01); C07D 471/10 (2006.01); C07D 487/04 (2006.01); C07D 487/10 (2006.01); C07D 491/044 (2006.01); C07D 491/052 (2006.01); C07F 9/6558 (2006.01)
CPC C07D 213/64 (2013.01) [A61K 31/551 (2013.01); C07D 401/04 (2013.01); C07D 401/06 (2013.01); C07D 401/10 (2013.01); C07D 401/12 (2013.01); C07D 401/14 (2013.01); C07D 405/12 (2013.01); C07D 405/14 (2013.01); C07D 413/06 (2013.01); C07D 413/12 (2013.01); C07D 413/14 (2013.01); C07D 471/04 (2013.01); C07D 471/10 (2013.01); C07D 487/04 (2013.01); C07D 487/10 (2013.01); C07D 491/044 (2013.01); C07D 491/052 (2013.01); C07F 9/65583 (2013.01)] 7 Claims
 
1. A compound of Formula I

OG Complex Work Unit Drawing
or a pharmaceutically acceptable salt thereof, where
A is
1) 6-membered monocyclic carbocycle unsubstituted or mono-substituted with R3 or di-substituted with R3 and R4, or
2) 10-membered bicyclic carbocycle unsubstituted or substituted with R3;
R1 is
1) C1-6 alkyl, or
2) 6-membered monocyclic carbocycle unsubstituted or substituted with R7;
R1a is H or CH3;
R2 is benzimidazole, which is unsubstituted or substituted with R16, R17 or R18;
R3 is tetrazole;
R4 is
1) —C(NH)NH2,
2) —NH2,
3) Halogen,
4) —C1-6 alkyl, unsubstituted or substituted with —OH, F or —NH2;
5) —C(O)OC1-6 alkyl,
6) —CF3,
7) —NO2,
8) —CN, or
9) —OC1-6 alkyl;
R7 is halogen, —CF3 or —OCF3;
R10 is
4-6-membered carbocycle either unsubstituted or substituted with —NHC(O)OH;
R14 is C1-6 alkyl unsubstituted or substituted with —OH, —C6H5, or —((CH2)n—O)m—CH3, where m is 1 or 2 and n is 1 or 2;
R16 is and R17 are each independently
1) 6-membered carbocycle unsubstituted or substituted with R20, or
2) 6-membered carbocycle unsubstituted or substituted with R19;
R18 is
1) —C(O)OC1-6 alkyl,
2) —C(O)OH,
3) halogen,
4) —P(O)(OC1-6 alkyl)(OC1-6 alkyl),
5) —P(O)(OH)2,
6) —SO2C1-6 alkyl,
7) —CN,
8) —CF3,
9) —C(O)NHR10,
10) —NHC(O)OR14,
11) —NHC(O)R10, or
12) —P(O)(NHC1-6 alkyl)(NH C1-6 alkyl);
R19 and R20 are each independently
1) halogen,
2) —SO2C1-6 alkyl,
3) —CF3,
4) —CN,
5) —OC1-6 alkyl,
6) —OCF3,
7) —C1-6 alkyl,
8) —C(O)NHR10,
9) —NHC(O)R10,
10) —P(O)(OH)2,
11) —P(O)(OC1-6 alkyl)(OC1-6 alkyl), or
12) —P(O)(NHC1-6 alkyl)(NH C1-6 alkyl).