Macrocycles as factor XIa inhibitors

A compound of Formula (II):

• or a stereoisomer, a tautomer, a pharmaceutically acceptable salt, or a solvate thereof, wherein:
• is independently selected from the group consisting of:
• L1 is independently selected from the group consisting of:
• a bond, —CHR5CHR5—, —CR5═CHR5—, —C≡C—, —OCH2—, —CHR5NH—, —CH2O—, —SCH2—, —SO2CH2—, —CH2NH—, and —CR5R5—;
• L is independently selected from the group consisting of:
• C3-8 alkylene and C3-8 alkenylene;
• wherein said alkylene and alkenylene are substituted with 0-2 R7 and optionally one or two of the carbon atoms of said alkylene and alkenylene may be replaced by O, CO, S, NH, N(C1-4 alkyl), CONH—, NHCO, OCONH, SO2NH, or CON(C1-4 alkyl);
• Y is independently selected from the group consisting of:
• CH2, CO, CH(C1-4 alkyl), C(C1-4 alkyl)2, O, S, NH, N(C1-4 alkyl), N(CO2(C1-4 alkyl)), —N(C1-4 alkyl)CH2—, —N(CO2(C1-4 alkyl))CH2—, —N(CH2CO2(C1-4 alkyl))CH2—, —CONH—, —NHCO—, —CONHCH2—, —CON(C1-4 alkyl)CH2—, —OCONH—, —OCON(C1-4 alkyl)-, —NHCONH—, and —SO2NH—;
• alternatively, L-Y is —C3-6 alkylene-CH═N—;
• R1 is, independently at each occurrence, selected from the group consisting of:
• halogen, C1-6 alkyl, C1-4 alkoxy, C1-4 alkylthio, C1-4 haloalkyl, OH, OCH2F, OCHF2, OCF3, CN, NH2, NH(C1-4 alkyl), N(C1-4 alkyl)2, CO2(C1-4 alkyl), CO(C1-4 alkyl), —OCH2CO2H, —CH2NH2, —CONH2, —CONH(C1-4 alkyl), —SO2NH2, and —C(═NH)NH2;
• R2 is independently a 5- to 6-membered heterocycle comprising carbon atoms and 1-4 heteroatoms selected from N, NH, O, and S(O)p, wherein said heterocycle is substituted with 0-2 R2a;
• R2a is, independently at each occurrence, selected from the group consisting of:
• halogen, C1-4 alkyl, —CH2OH, C1-4 alkoxy, OH, CF3, CN, NH2, CO2H, CO2(C1-4 alkyl), COC1-4 alkyl, —CONH2, —CONH(C1-4 alkyl), and —CON(C1-4 alkyl)2;
• R3 is independently selected from the group consisting of:
• H, halogen, OH, NH2, CN, CF3, C1-4 alkyl, C1-4 alkoxy, —CH2OH, CO2H, CO2(C1-4 alkyl), C(O)NH2, —C(O)NH(C1-4 alkyl), —C(O)N(C1-4 alkyl)2, —CH2CO2H, and C3-6 cycloalkyl;
• R4 is independently selected from the group consisting of:
• H and C1-4 alkyl;
• R5 is, independently at each occurrence, selected from the group consisting of:
• H, halogen, OH, and C1-4 alkyl;
• R6 is, independently at each occurrence, selected from the group consisting of:
• halogen, C1-4 alkyl, CN, OH, CF3, CO2H, CO2(C1-4 alkyl), —CH2CO2H, —(CH2)2CO2H, —CH2CO2(C1-4 alkyl), —(CH2)2CO2(C1-4 alkyl), NH2, —CH2NH2, —NHCO(C1-4 alkyl), —NHCO2(C1-4 alkyl), —NHCO2(CH2)2O(C1-4 alkyl), —NHCO2(CH2)3O(C1-4 alkyl), —NHCO2CH2CH(C1-4 alkyl)O(C1-4 alkyl), —NHCO2(CH2)2OH, —NHCO2(CH2)2NH2, —NHCO2CH2CO2H, —CH2NHCO2(C1-4 alkyl), —NHC(O)NH(C1-4 alkyl), —NHC(O)N(C1-4 alkyl)2, —NHSO2(C1-4 alkyl), —SO2NH(CH2)2OH, —SO2NH(CH2)2O(C1-4 alkyl), —CONH(CH2)2O(C1-4 alkyl), CONH2, CONH(C1-4 alkyl), CON(C1-4 alkyl)2, —CH2CONH2, —NHCO2(CH2)2N(C1-4 alkyl)2, —NHCOCF3, and —NHCO2(CH2)0-1R9;
• R7 is, independently at each occurrence, selected from the group consisting of:
• halogen, OH, C1-4 haloalkyl, C1-4 alkoxy, CH2OH, CH2O(C1-4 alkyl), CO2H, CO2(C1-4 alkyl), CO2(CH2)2O(C1-4 alkyl)), CO2CH2CF3, CO2(CH2)2SO2(C1-4 alkyl), CH2CO2H, CH2CO2(C1-4 alkyl), CONH2, CONH(C1-4 alkyl), CON(C1-4 alkyl)2, —OCO(C1-4 alkyl), —CH2NH(CH2)2O(C1-4 alkyl), —CO2(CH2)2N(C1-4 alkyl)2, —CONH(CH2)2O(C1-4 alkyl), —CONH(CH2)2N(C1-4 alkyl)2, —CON(C1-4 alkyl)(CH2)2O(C1-4 alkyl), —CONH(CH2)2N(C1-4 alkyl)2, —CON(C1-4 alkyl)(CH2)2N(C1-4 alkyl)2, —CONH(C1-4 alkoxy), —CONHBn, —CONH(OBn), —(CH2)1-3Ph, C1-4 alkyl, and —(CH2)0-1—(CO)0-1-(W)0-1-(CH2)0-2-(4- to 6-membered heterocycle comprising carbon atoms and 1-4 heteroatoms selected from N, NH, N(C1-4 alkyl), O, and S(O)p;
• wherein said heterocycle is substituted with 0-2 R8;
• R8 is, independently at each occurrence, selected from the group consisting of:
• halogen, OH, CHF2, CF3, C1-4 alkoxy, and C1-4 alkyl;
• R9 is a 4- to 6-membered heterocycle comprising:
• carbon atoms and 1-4 heteroatoms selected from N, NH, N(C1-4 alkyl), N(CO2(C1-4 alkyl)), O, and S(O)p;
• W is independently selected from the group consisting of:
• O and NH;
• and
• p is, independently at each occurrence, selected from the group consisting of:
• 0, 1, and 2.