Arylpropionamide, arylacrylamide, arylpropynamide, or arylmethylurea analogs as factor XIa inhibitors

A compound of Formula (I):

• or a stereoisomer, a tautomer, or a pharmaceutically acceptable salt thereof, wherein:
• A is phenyl substituted with 0-1 R1 and 0-3 R2;
• L1 is —CH(R5)CH2—, —CH(NR7R8)CH2—, —C(R5)═CH—, —C≡—, —OCH2—, —CR5R6NH—, —CH2O—, —SCH2—, —SO2CH2—, —CH2NR10—, or —NHNH—;
• provided that when L1 is —CH2O—, then A is other than an unsubstituted phenyl;
• R1 is, independently at each occurrence, F, Cl, Br, I, OCF3, CF3, —(CH2)rORa, —(CH2)rSRa, CN, —(CH2)rNR7R8, —C(═NR8)NR8R9, —C(O)NR8R9, —S(O)pNR8R9, or C1-6 alkyl substituted with 0-1 R1a;
• R1a is F, OCF3, CF3, ORa, SRa, CN, —NR7R8, —C(O)NR8R9, —NR8C(O)Rc, —S(O)pNR8R9, —NR8SO2Rc, or —(CF2)rCF3;
• R2 is, independently at each occurrence, ═O, F, Cl, Br, OCF3, CF3, CHF2, CN, NO2, —(CH2)rORa, —(CH2)rSRa, —(CH2)rC(O)Ra, —(CH2)rC(O)ORa, —(CH2)rOC(O)Ra, —(CH2)rNR7R8, —(CH2)rC(O)NR8R9, —(CH2)rNR8C(O)Rc, —(CH2)rNR8C(O) ORc, —NR8C(O)NR8Rc, —S(O)pNR8R9, —NR8S(O)pRc, —S(O)Rc, —S(O)2Rc, C1-6 alkyl substituted with 0-1 R2a, —(CH2)r-3-7 membered carbocycle optionally substituted with 0-2 R2b, or —(CH2)r-5-7 membered heterocycle comprising carbon atoms and 1-4 heteroatoms selected from N, O, and S(O)p, wherein said heterocycle is substituted with 0-2 R2b;
• R2a is F, OCF3, CF3, ORa, SRa, CN, —NR7R8, —C(O)NR8R9, —NR8C(O)Rc, —NR8C(O) ORc, —NR8C(O)NR8Rc, —S(O)pNR8R9, —NR8SO2Rc, or —(CF2)rCF3;
• R2b is, independently at each occcurence, ═O, F, Br, Cl, OCF3, CF3, —(CH2)rORa, —(CH2)rSRa, —(CH2)rCN, —(CH2)rNR7R8, —(CH2)rC(O)ORa, —(CH2)rOC(O)Ra, —(CH2)rC(O)NR8R9, —(CH2)rNR8C(O)Rc, —(CH2)rNR8C(O)ORc, —(CH2)rS(O)pNR8R9, —(CH2)rNR8SO2Rc, C1-4 alkyl or —(CF2)rCF3;
• R3 is, independently at each occurrence, —(CH2)r—C3-10 carbocycle substituted with 0-3 R3a and 0-1 R3d, or —(CH2)r-5- to 12-membered heterocycle comprising:
• carbon atoms and 1-4 heteroatoms selected from N, O, and S(O)p, wherein said heterocycle is substituted with 0-3 R3a and 0-1 R3d;
• R3a is, independently at each occurrence, ═O, ═NR8, F, Cl, Br, I, OCF3, CF3, —(CH2)rCN, NO2, —(CH2)rOR3b, —(CH2)rSR3b, —(CH2)rNR7R8, —NHC(O)NR8R9, —(CH2)rC(O) OR3b, —C(O)C1-4 alkyl, —SO2NHR3b, —SO2NHCOR3c, —SO2NHCO2R3c, —CONHSO2R3c, —(CH2)rNR8C(O)R3b, —(CH2)rNR8CO2R3c, —(CH2)rS(O)pNR8R9, —(CH2)rNR8S(O)pR3c, —NHSO2CF3, —S(O)R3c, —S(O)2R3c, —(CH2)rOC(O)R3b, —(CH2)rC(O)NR8R9, —(CH2)rOC(O)NR8R9, —NHCOCF3, —NHSO2R3c, —CONHOR3b, C1-4 haloalkyl, C1-4 haloalkyloxy-, C1-6 alkyl substituted by R3e, C2-6 alkenyl substituted by R3e, C1-6 alkynyl substituted by R3e, C3-6 cycloalkyl substituted by 0-1 R3d, —(CH2)r—C6-10 carbocycle substituted by 0-3 R3d or —(CH2)r-5- to 10-membered heterocycle comprising:
• carbon atoms and 1-4 heteroatoms selected from N, O, and S(O)p, wherein said heterocycle is substituted with 0-3 R3d;
• alternately, when two R3a groups are substituted on adjacent atoms, they can be taken together with the atoms to which they are attached to form a C3-10 carbocycle substituted with 0-2 R3d, or a 5- to 10-membered heterocycle comprising:
• carbon atoms and 1-4 heteroatoms selected from N, O, and S(O)p, wherein said heterocycle is substituted with 0-2 R3d;
• R3b is, independently at each occurrence, H, C1-6 alkyl substituted with 0-2 R3d, C2-6 alkenyl substituted with 0-2 R3d, C2-6 alkynyl substituted with 0-2 R3d, —(CH2)r—C3-10 carbocycle substituted with 0-3 R3d, or —(CH2)r-5- to 10-membered heterocycle comprising:
• carbon atoms and 1-4 heteroatoms selected from N, O, and S(O)p, wherein said heterocycle is substituted with 0-3 R3d;
• R3c is, independently at each occurrence, C1-6 alkyl substituted with 0-2 R3d, C2-6 alkenyl substituted with 0-2 R3d, C2-6 alkynyl substituted with 0-2 R3d, —(CH2)r—C3-10 carbocycle substituted with 0-3 R3d, or —(CH2)r-5- to 10-membered heterocycle comprising:
• carbon atoms and 1-4 heteroatoms selected from N, O, and S(O)p, wherein said heterocycle is substituted with 0-3 R3d;
• R3d is, independently at each occurrence, H, ═O, F,Cl, Br, CN, NO2, —(CH2)rNR7R8, —(CH2)rORa, —C(O)Ra, —C(O)ORa, —OC(O)Ra, —NR8C(O)Rc, —C(O)NR8R9, —S(O)2NR8R9, —NR7R8, —NR8S(O)2NR8R9, —NR8S(O)2Rc, —S(O)pRc, —(CF2)rCF3, C1-6 alkyl substituted with 0-2 Re, C2-6 alkenyl substituted with 0-2 Re, C2-6 alkynyl substituted with 0-2 Re, —(CH2)r—C3-10 carbocycle substituted with 0-3 Rd, or —(CH2)r-5- to 10-membered heterocycle comprising:
• carbon atoms and 1-4 heteroatoms selected from N, O, and S(O)p, wherein said heterocycle is substituted with 0-3 Rd;
• R3e is, independently at each occurrence, H, —(CH2)rORa, F, ═O, CN, NO2, —(CH2)rNR7R8, —C(O)Ra, —C(O)ORa, —OC(O)Ra, —NR8C(O) Rc, —C(O)NR8R9, —S(O)2NR8R9, —NR8S(O)2NR8R9, —NR8S(O)2Rc, —S(O)pRc, —(CF2)rCF3, —(CH2)r—C3-10 carbocycle substituted with 0-3 Rd, or —(CH2)r-5- to 10-membered heterocycle comprising:
• carbon atoms and 1-4 heteroatoms selected from N, O, and S(O)p, wherein said heterocycle is substituted with 0-3 Rd;
• R4 is, independently at each occurrence, H, F, Cl, Br, I, OCF3, CF3, CN, NO2, —(CH2)rORa, —(CH2)rSRa, —(CH2)rC(O)Ra, —(CH2)rC(O)ORa, —OC(O)Ra, —(CH2)rNR7R8, —NR8(CH2)rC(O)ORa, —(CH2)rC(O)NR8R9, —(CH2)rNR8C(O)Rc, —(CH2)rNR8C(O)2Rb, —(CH2)rNR8C(O)NR8R9, —S(O)pNR8R9, —NR8S(O)pRc, —S(O)2Rc, or C1-4 alkyl substituted with 0-2 R4a;
• R4a is, independently at each occurrence, H, F, ═O, C1-6 alkyl, ORa, SRa, CF3, CN, NO2, —C(O)Ra, —C(O)ORa, —NR7R8, —C(O)NR8R9, —NR8C(O)Rc, —S(O)pNR8R9, —NR8S(O)pRc, —S(O)Rc, or —S(O)2Rc;
• R5 is, independently at each occurrence, H, F, CF3, —(CH2)rORa, ═O, —(CH2)rNR7R8, —S(O)pNR8R9, —(CH2)rCO2Ra, —(CH2)rCONR8R9, or C1-4 alkyl;
• R6 is, independently at each occurrence, H, F, or C1-4 alkyl;
• R7 is, independently at each occurrence, H, C1-6 alkyl, —(CH2)n—C3-10 carbocycle, —(CH2)n-(5- to 10-membered heteroaryl), —C(O)Rc, —CHO, —C(O)2Rc, —S(O)2Rc, —CONR8Rc, —OCONHRc, —C(O)O—(C1-4 alky)OC(O)—(C1-4 alkyl), or —C(O)O—(C1-4 alky)OC(O)—(C6-10 aryl);
• wherein said alkyl, carbocycle, heteroaryl, and aryl are substituted with 0-2 Rf;
• wherein said heteroaryl comprises:
• carbon atoms and 1-4 heteroatoms selected from N, O, and S(O)p;
• R8 is, independently at each occurrence, H, C1-6 alkyl, —(CH2)n-phenyl, or —(CH2)n-5- to 10-membered heterocycle comprising:
• carbon atoms and 1-4 heteroatoms selected from N, O, and S(O)p;
• wherein said alkyl, phenyl and heterocycle are optionally substituted with 0-2 Rf;
• alternatively, R7 and R8, when attached to the same nitrogen, combine to form a 5- to 10-membered heterocycle comprising:
• carbon atoms and 0-3 additional heteroatoms selected from N, O, and S(O)p, wherein said heterocycle is substituted with 0-2 Rf;
• R8a is H or C1-4 alkyl;
• R9 is, independently at each occurrence, H, C1-6 alkyl, or —(CH2)n-phenyl;
• wherein said alkyl and phenyl are optionally substituted with 0-2 Rf;
• alternatively, R8 and R9, when attached to the same nitrogen, combine to form a 5- to 12-membered heterocycle comprising:
• carbon atoms and 0-2 additional heteroatoms selected from N, O, and S(O)p, wherein said heterocycle is substituted with 0-2 Rd;
• R10 is, independently at each occurrence, H or C1-6 alkyl substituted with 0-3 R10a;
• R10a is, independently at each occurrence, H, ═O, C1-4 alkyl, ORa, SRa, F, CF3, CN, NO2, —C(O)Ra, —C(O)ORa, —C(O)NR8R9, —NR8C(O)Rc, —S(O)pNR8R9, —NR8S(O)pRc, or —S(O)pRc;
• R11 is —C(O)NR8R9, —CH2C(O)NR8R9, —CH2CH2C(O)NR8R9, —C(O)Ra, —CH2C(O)Ra, —CH2CH2C(O)Ra, —C(O)ORa, —CH2C(O)ORa, and —CH2CH2C(O)ORa;
• Ra is, independently at each occurrence, H, CF3, C1-6 alkyl, —(CH2)r—C3-7 cycloalkyl, —(CH2)r—C6-10 aryl, or —(CH2)r-5- to 10-membered heterocycle comprising carbon atoms and 1-4 heteroatoms selected from N, O, and S(O)p, wherein said cycloalkyl, aryl or heterocycle groups are optionally substituted with 0-2 Rf;
• Rb is, independently at each occurrence, CF3, OH, C1-4 alkoxy, C1-6 alkyl, —(CH2)r—C3-10 carbocycle substituted with 0-2 Rd, or —(CH2)r-5- to 10-membered heterocycle comprising:
• carbon atoms and 1-4 heteroatoms selected from N, O, and S(O)p and substituted with 0-3 Rd;
• Rc is, independently at each occurrence, CF3, C1-6 alkyl substituted with 0-2 Rf, C3-6 cycloalkyl substituted with 0-2 Rf, C6-10 aryl, 5- to 10-membered heteroaryl, (C6-10 aryl)-C1-4 alkyl, or (5-to 10-membered heteroaryl)-C1-4 alkyl, wherein said aryl is substituted with 0-3 Rf and said heteroaryl comprises:
• carbon atoms and 1-4 heteroatoms selected from N, O, and S(O)p and substituted with 0-3 Rf;
• Rd is, independently at each occurrence, H, ═O, ═NR8, ORa, F, Cl, Br, I, CN, NO2, —NR7R8, —C(O)Ra, —C(O)ORa, —OC(O)Ra, —NR8C(O)Rc, —C(O)NR8R9, —SO2NR8R9, —NR8SO2NR8R9, —NR8SO2—C1-4 alkyl, —NR8SO2CF3, —NR8SO2-phenyl, —S(O)2CF3, —S(O)p—C1-4 alkyl, —S(O)p-phenyl, —(CF2)rCF3, C1-6 alkyl substituted with 0-2 Re, C2-6 alkenyl substituted with 0-2 Re, or C2-6 alkynyl substituted with 0-2 Re;
• Re is, independently at each occurrence, ═O, ORa, F, Cl, Br, I, CN, NO2, —NR7R8, —C(O) Ra, —C(O)ORa, —NR8C(O)Rc, —C(O)NR8R9, —SO2NR8R9, —NR8SO2NR8R9, —NR8SO2—C1-4 alkyl, —NR8SO2CF3, —NR8SO2-phenyl, —S(O)2CF3, —S(O)p—C1-4 alkyl, —S(O)p-phenyl, or —(CF2)rCF3;
• Rf is, independently at each occurrence, H, ═O, —(CH2)rORg, F, Cl, Br, I, CN, NO2, —NRgRg, —C(O)Rg, —C(O)ORg, —NRgC(O)Rg, —C(O)NRgRg, —SO2NRgRg, —NRgSO2NRgRg, —NRgSO2—C1-4 alkyl, —NRgSO2CF3, —NRgSO2-phenyl, —S(O)2CF3, —S(O)p—C1-4 alkyl, —S(O)p-phenyl, —(CF2)rCF3, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, —(CH2)n-phenyl, or —(CH2),n-5- to 10-membered heterocycle comprising carbon atoms and 1-4 heteroatoms selected from N, O, and S(O)p;
• Rg is, independently at each occurrence, H, C1-6 alkyl, or —(CH2),n-phenyl;
• n, at each occurrence, is selected from 0, 1, 2, 3, and 4;
• p, at each occurrence, is selected from 0, 1, and 2;
• and
• r, at each occurrence, is selected from 0, 1, 2, 3, and 4.