Benzopiperazine compositions as BET bromodomain inhibitors

A process of preparing a compound of Formula (VI):

• or a pharmaceutically acceptable salt thereof, wherein:
• R10 is independently selected from the group consisting of C1-C6 alkyl, C1-C6 alkoxy, C1-C6 hydroxyalkyl, C1-C6 haloalkyl, C1-C6 haloalkoxy, —OR, —NRaRi, —CN, —(CRkRl)nS(O)2Ri, —(CRkRl)nNRaS(O)2Ri, —(CRkRl)nS(O)2NRaRi, —(CRkRl)nC(O)ORa, —(CRkRl)nC(O)Ri, —(CRkRl)nC(O)NRaRi, —(CRkRl)nRi, —(CRkRl)nNRaC(O)NRb, and —(CRkRl)nNRaC(O)ORb, wherein each alkyl is substituted with one or more R11;
• each R11 is independently selected from halogen, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, hydroxy, —CN, C1-C6 hydroxyalkyl, —(CRkRl)mNH2, C1-C6 alkylamino, C1-C6 dialkylamino, —C(O)NRaRb, —C(O)ORa, —C(O)Ra, —S(O)2Ra, —C(O)H, —NRaC(O)ORa, —NRaC(O)C1-C6 alkyl, and oxo;
• or
• two R11 together can form a heterocycloalkyl ring;
• Ra and Rb are each independently hydrogen, C1-C6 alkyl, C1-C4 alkyl(aryl), or aryl;
• Rd is C1-C6 alkyl, C1-C6 haloalkyl, C3-C7 cycloalkyl, aryl, heteroaryl, or heterocycloalkyl, wherein cycloalkyl, aryl, heteroaryl, and heterocycloalkyl are optionally substituted with one or more R12;
• Ri is hydrogen, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 hydroxyalkyl, C1-C6 haloalkyl, —(CH2)qN(H)C1-C6 alkyl, —(CH2)qN(C1-C6 alkyl)2, —(CRkRl)mC3-C7 cycloalkyl, —(CRkRl)maryl, —(CRkRl)mheteroaryl, or —(CRkRl)mheterocycloalkyl, wherein alkyl, cycloalkyl, aryl, heteroaryl, and heterocycloalkyl are optionally substituted with one or more R11;
• each R12 is independently selected from C1-C6 alkyl, halogen, —CN, C1-C6 alkoxy, C1-C6 haloalkyl, C1-C6 haloalkoxy, hydroxy, —NO2, —NH2, —CH2NH2, —(CH2)qN(C1-C6 alkyl)2, C1-C6 alkylamino, C1-C6 dialkylamino, —O(CH2)qN(H)C1-C6 alkyl, —O(CH2)qN(C1-C6 alkyl)2, aryl, heteroaryl, —NH-heteroaryl, —O-aryl, —S(O)p—C1-C6 alkyl, —S(O)p—N(H)C1-C6 alkyl, —S(O)p—N(C1-C6 alkyl)2, —C(O)C1-C6 alkyl, —C(O)OC1-C6 alkyl, —NHC(O)(C1-C6 alkyl), and oxo, wherein aryl and heteroaryl are optionally substituted with one or more substituents selected from C1-C6 alkyl, halogen, —CN, C1-C6 alkoxy, hydroxy, —NO2, —NH2, C1-C6 alkylamino, or C1-C6 dialkylamino;
• or
• two R12 together with the carbon to which they are attached form a 4- to 6-membered heterospirocycle;
• or
• two R12 together when on adjacent carbons form a C4-C6 cycloalkyl optionally substituted with one or more R13;
• or
• two R12 together when on adjacent carbons form an aryl optionally substituted with one or more R13;
• or
• two R12 together when on adjacent carbons form a heteroaryl optionally substituted with one or more R13;
• or
• two R12 together when on adjacent carbons form a heterocycloalkyl optionally substituted with one or more R13;
• or
• R12 with the carbon to which it is attached and the adjacent carbon form a C3 cycloalkyl optionally substituted with one or more R13;
• each R13 is independently at each occurrence selected from C1-C6 alkyl, halogen, —CN, C1-C6 alkoxy, C1-C6 haloalkyl, C1-C6 haloalkoxy, hydroxy, —NO2, —NH2, —CH2NH2, —(CH2)qN(C1-C6 alkyl)2, C1-C6 alkylamino, C1-C6 dialkylamino, —O(CH2)qN(H)C1-C6 alkyl, —O(CH2)qN(C1-C6 alkyl)2, aryl, heteroaryl, —NH-heteroaryl, —O-aryl, —S(O)p—C1-C6 alkyl, —S(O)p—N(H)C1-C6 alkyl, —S(O)p—N(C1-C6 alkyl)2, —C(O)C1-C6 alkyl, —NHC(O)(C1-C6 alkyl), or oxo, wherein aryl and heteroaryl are optionally substituted with one or more substituents selected from consisting of C1-C6 alkyl, halogen, —CN, C1-C6 alkoxy, hydroxy, —NO2, —NH2, C1-C6 alkylamino, and C1-C6 dialkylamino;
• Rk and Rl are each independently at each occurrence selected from —H, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, or halogen;
• each m, n, and p is independently at each occurrence 0, 1, or 2;
• and
• each q is independently at each occurrence 1, 2, 3 or 4,
• wherein the process comprises a step of contacting an aryl bromide compound:
• with a boronic ester compound:
• in the presence of a palladium catalyst to give the compound of Formula (VI).