Process for preparing Substituted Indole Compounds

1. A process for preparing a compound of Formula (I):

wherein said process comprises the steps:

(A) preparing a solution, wherein said solution comprises: (a) compound of Formula (i):

(b) a photocatalyst, selected from fac-Ir(ppy) 3 , fac-Ir(dF-ppy) 3 , Ir(ppy) 2 (dtbpy), [Ir(dF-CF 3 -ppy) 2 (dtbpy)(PF 6 ), Ir(ppy) 3 , Ir(dF-CF 3 -ppy) 2 (dtbpy), [Ru(bpm) 3 ]Cl 2 , [Ru(bpy) 3 ]Cl 2 , [Ru(bpz) 3 ]Cl 2 and [Ru(phen)]Cl 2 , or a salt thereof, (c) an oxidizing agent, selected from an organic peroxyester, and (d) an organic solvent, selected from acetonitrile, N,N-dimethylformamide, N,N-dimethylacetamide and dimethylsulfoxide;

(B) exposing the solution of Step A to light having a wavelength in the UV/Visible spectrum, for a time and at a temperature sufficient to provide a compound of formula (I),

wherein:

R 1 represents up to 4 optional benzene ring substituents, which can be the same or different, and are each selected from C 1 -C 6 alkyl, halo, —OTf, C 3 -C 7 cycloalkyl, C 6 -C 10 aryl, 5 or 6-membered monocyclic heteroaryl and 9 or 10-membered bicyclic heteroaryl;

R 2 is H or halo;

R 3 is selected from H, C 1 -C 6 alkyl, C 3 -C 7 cycloalkyl, C 6 -C 10 aryl, 5 or 6-membered monocyclic heteroaryl, 9 or 10-membered bicyclic heteroaryl, 4 to 7-membered monocyclic heterocycloalkyl and 8 to 12-membered bicyclic heterocycloalkyl, wherein said C 3 -C 7 cycloalkyl group, said C 6 -C 10 aryl group, said 5 or 6-membered monocyclic heteroaryl group, said 9 or 10-membered bicyclic heteroaryl group, said 4 to 7-membered monocyclic heterocycloalkyl group and 8 to 12-membered bicyclic heterocycloalkyl group can be optionally substituted with one or more R 5 groups, which can be the same or different;

R 4 is selected from H, C 1 -C 6 alkyl and C(O)—(C 1 -C 6 alkyl), or when R 3 is phenyl, R 4 can be a group having the formula CH(R 6 )—O—, wherein the oxygen atom of the group of formula —CH(R 6 )—O— is attached to a meta carbon atom of said R 3 phenyl group;

each occurrence of R 5 is independently selected from C 1 -C 6 alkyl, halo, —OTf, C 1 -C 6 haloalkyl, C 1 -C 6 hydroxyalkyl, —CN, —O—(C 1 -C 6 alkyl), —O—(C 6 -C 10 aryl), —O—(C 1 -C 6 alkylene)-O—(C 1 -C 6 alkyl), —O—(C 1 -C 6 haloalkyl), —N(R 8 ) 2 , —S—(C 1 -C 6 alkyl), —S(O) 2 —(C 1 -C 6 alkyl), —NHS(O) 2 —(C 1 -C 6 alkyl), —OC(O)R 7 , —C(O)OR 7 , —C(O)R 7 , —C(O)N(R 8 ) 2 , and —NHC(O)R 7 ;

R 6 is selected from C 1 -C 6 alkyl, phenyl and 5 or 6-membered heteroaryl, wherein said heteroaryl group can be optionally substituted with C 1 -C 6 alkyl or C 3 -C 7 cycloalkyl;

each occurrence of R 7 is independently selected from H, C 1 -C 6 alkyl, C 3 -C 7 cycloalkyl, C 6 -C 10 aryl and 5 or 6-membered monocyclic heteroaryl; and

each occurrence of R 8 is independently selected from H and C 1 -C 6 alkyl.

2. The process of claim 1 , wherein the organic peroxyester is tert-butyl peroxybenzoate.

3. The process of claim 1 , wherein in Step B, the UV-visible light has a wavelength of from 350 nm to 500 nm.

4. The process of claim 1 , wherein in Step B, the solution is exposed to the UV-visible light for a time period of from 10 minutes to 2 hours.

5. The process of claim 1 , wherein in Step B, the solution is exposed to the UV-visible light for a time period of from 30 minutes to 1 hour.

6. The process of claim 1 , wherein the solution of Step A is maintained at a temperature of from −20° C. to 25° C. throughout the entirety of Step B.

7. The process of claim 1 , wherein for the compounds of formulas (i) and (I), R 1 is halo.

8. The process of claim 1 , wherein for the compounds of formulas (i) and (I), R 2 is H.

9. The process of claim 1 , wherein for the compounds of formulas (i) and (I), R 3 is phenyl and R 4 is —CH(R 6 )—O—, wherein the oxygen atom of the group of formula —CH(R 6 )—O— is attached to a meta carbon atom of said phenyl group.

10. The process of claim 1 , wherein for the compounds of formulas (i) and (I), R 4 is selected from H, C 1 -C 6 alkyl and —C(O)—(C 1 -C 6 alkyl).

11. The process of claim 1 , wherein the compound of formula (i) has the formula (i′):

and the compound of formula (I) has the formula (I′):

wherein R 1 and R 5b are each halo, R 5a is H or F, and R a is phenyl or 5 or 6-membered heteroaryl, wherein said heteroaryl group is optionally substituted with C 1 -C 6 alkyl or C 3 -C 7 cycloalkyl.

12. The process of claim 11 , wherein R 1 and R 5b are each Br, R 5a is H, and R a is phenyl.

13. The process of claim 11 , wherein R 1 and R 5b are each Br, R 5a is F, and R a is thiazolyl, optionally substituted with a cyclopropyl group.