Modulators of ATP-binding cassette transporters

1. A process of preparing compounds of the following formula Ic:

wherein,

R 1 is —Z A R 4 , wherein each Z A is independently a bond or an optionally substituted branched or straight C 1-6 aliphatic chain wherein up to two carbon units of Z A are optionally and independently replaced by —CO—, —CS—, —CONR A —, —CONR A NR A —, —CO 2 —, —OCO—,

—NR A CO 2 —, —O—, —NR A CONR A —, —OCONR A —, —NR A NR A —, —NR A CO—, —S—, —SO—, —SO 2 —, —NR A —, —SO 2 NR A —, —NR A SO 2 —, or —NR A SO 2 NR A —,

Each R 4 is independently R A , halo, —OH, —NH 2 , —NO 2 , —CN, or —OCF 3 ,

Each R A is independently hydrogen, an optionally substituted aliphatic, an optionally substituted cycloaliphatic, an optionally substituted heterocycloaliphatic, an optionally substituted aryl, or an optionally substituted heteroaryl;

Each R 2 is independently —Z B R 5 , wherein each Z B is independently a bond or an optionally substituted branched or straight C 1-6 aliphatic chain wherein up to two carbon units of Z 8 are optionally and independently replaced by —CO—, —CS—, —CONR B —, —CONR B NR B —, —CO 2 —, —OCO—, —NR B CO 2 —, —O—, —NR B CONR B —, OCONR B —, —NR B NR B —, —NR B CO—, —S—, SO—, —SO 2 —, —NR B —, —SO 2 NR B —, —NR B SO 2 —, or —NR B SO 2 NR B —,

Each R 5 is independently R B , halo, —OH, —NH 2 , —NO 2 , —CN, —CF 3 , or —OCF 3 ,

Each R B is independently hydrogen, an optionally substituted aliphatic, an optionally substituted cycloaliphatic, an optionally substituted heterocycloaliphatic, an optionally substituted aryl, or an optionally substituted heteroaryl,

Or, any two adjacent R 2 groups together with the atoms to which they are attached form an optionally substituted carbocycle or an optionally substituted heterocycle;

Ring A is an optionally substituted 3-7 membered monocyclic ring having 0-3 heteroatoms selected from N, O, and S;

Ring B is a group having formula Ia:

or a pharmaceutically acceptable salt thereof, wherein

p is 0-2,

Each R 3 and R′ 3 is independently —Z C R 6 , where each Z C is independently a bond or an optionally substituted branched or straight C 1-6 aliphatic chain wherein up to two carbon units of Z C are optionally and independently replaced by —CO—, —CS—, —CONR C —, —CONR C NR C —, —CO 2 —, —OCO—, —NR C CO 2 —, —O—, —NR C CONR C —, —OCONR C —, —NR C NR C —, —NR C CO—, —S—, —SO—, —SO 2 —, —NR C —, —SO 2 NR C —, —NR C SO 2 —, or —NR C SO 2 NR C —,

Each R 6 is independently R C , halo, —OH, —NH 2 , —NO 2 , —CN, or —OCF 3 ,

Each R C is independently hydrogen, an optionally substituted aliphatic, an optionally substituted cycloaliphatic, an optionally substituted heterocycloaliphatic, an optionally substituted aryl, or an optionally substituted heteroaryl,

Or, any two adjacent R 3 groups together with the atoms to which they are attached form an optionally substituted heterocycle; and

n is 1-3;

comprising converting the acid of the following formula:

to the corresponding acid chloride of the following formula:

wherein R 2 , n, and ring A are as defined above, and

coupling the acid chloride with an amine of the following formula:

wherein R 1 and Ring B are as defined above

or alternatively, reacting the acid with a coupling reagent to provide an active ester and coupling the active ester with an amine of the aforementioned formula.

2. The process of claim 1 , wherein n is 2 and two adjacent R 2 groups together with the atoms to which they are attached form an optionally substituted heterocycle.

3. The process of claim 2 , wherein n is 2 and two adjacent R 2 groups together with the atoms to which they are attached form

ring A is a cyclopropyl ring;

R 1 is H;

p is 2 and one R 3 is halo or H and the other R 3 is —C(CH 3 ) 2 CH 2 OH; and R′ 3 is —CH 2 CH(OH)CH 2 OH.