Synthesis of ETP derivatives

Patent metadata

Field	Value
Publication number	US-11230560-B2
Application number	US-201816615300-A
Country	US
Kind code	B2
Filing date	May 22, 2018
Priority date	May 22, 2017
Publication date	Jan 25, 2022
Grant date	Jan 25, 2022

Abstract

Provided herein, inter alia, is the synthesis of ETP derivatives. The synthetic methods described herein include converting a ring bridging trisulfide compound of formulato a ring bridging disulfide compound of formulaAlso provided herein are compositions comprising thereof.

First claim

What is claimed is:

1. A method for converting a ring bridging trisulfide compound to a ring bridging disulfide compound, comprising combining the ring bridging trisulfide compound with a non-nucleophilic base, thereby affording the corresponding ring bridging disulfide compound, wherein the ring bridging trisulfide compound is of formula (Ia):

and the ring bridging disulfide compound is of formula (Ib):

wherein:
R 1 is hydrogen, halogen, —N 3 , —CF 3 , —CCl 3 , —CBr 3 , —CI 3 , —CN, —CHO, —OR 33A , —NR 34A R 35A , —COOR 33A , —CONR 34A R 35A , —NO 2 , —SR 36A , —SO n1 R 34A , —SO n1 OR 34A , —SO n1 NR 34A R 35A , —NHNR 34A R 35A , —ONR 34A R 35A , —NHC(O)NHNR 34A R 35A , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl,
R 2 is hydrogen, halogen, —N 3 , —CF 3 , —CCl 3 , —CBr 3 , —CI 3 , —CN, —CHO, —OR 33B , —NR 34B R 35B , —COOR 33B , —CONR 34B R 35B , —NO 2 , —SR 36B , —SO n2 R 34B , —SO n2 OR 34B , —SO n2 NR 34B R 35B , —NHNR 34B R 35B , —ONR 34B R 35B , —NHC(O)NHNR 34B R 35B , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
R 3 is hydrogen, halogen, —N 3 , —CF 3 , —CCl 3 , —CBr 3 , —CI 3 , —CN, —CHO, —OR 33C , —NR 34C R 35C , —NR 34C R 35C , —COOR 33C , —CONR 34C R 35C , —NO 2 , —SR 36C , —SO n3 R 34C , —SO n3 OR 34C , —SO n3 NR 34C R 35C , —NHNR 34C R 35C , —ONR 34C R 35C , —NHC(O)NHNR 34C R 35C , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
R 4 is hydrogen, halogen, —N 3 , —CF 3 , —CCl 3 , —CBr 3 , —CI 3 , —CN, —CHO, —OR 33D , —NR 34 R 35D , —COOR 33D , —CONR 34D R 35D , —NO 2 , —SR 36D , —SO n4 R 34D , —SO n4 OR 34D , —SO n4 NR 34D R 35D , —NHNR 34D R 35D , —ONR 34D R 35D , —NHC(O)NHNR 34D R 35D , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
R 5 is hydrogen, halogen, —N 3 , —CF 3 , —CCl 3 , —CBr 3 , —CI 3 , —CN, —CHO, —OR 33E , —NR 34E R 35E , —COOR 33E , —CONR 34E R 35E , —NO 2 , —SR 36E , —SO n5 R 34E , —SO n5 OR 34E , —SO n5 NR 34E R 35E , NHNR 34E R 35E , —ONR 34E R 35E , —NHC(O)NHNR 34E R 35E substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
R 6 is hydrogen, halogen, —N 3 , —CF 3 , —CCl 3 , —CBr 3 , —CI 3 , —CN, —CHO, —OR 33F , —NR 34F R 35F , —COOR 33F , —CONR 34F R 35F , —NO 2 , —SR 36F , —SO n6 R 34F , —SO n6 OR 34F , —SO n6 NR 34F R 35F , NHNR 34F R 35F , —ONR 34F R 35F , —NHC(O)NHNR 34F R 35F , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
R 16 is hydrogen, halogen, —N 3 , —CF 3 , —CCl 3 , —CBr 3 , —CI 3 , —CN, —CHO, —OR 33G , —NR 34G R 35G , —COOR 33G , —CONR 34G R 35G , —NO 2 , —SR 36G , —SO n7 R 34G , —SO n7 OR 34G , —SO n7 NR 34G R 35G , NHNR 34G R 35G , —ONR 34G R 35G , —NHC(O)NHNR 34G R 35G , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
R 18 is hydrogen, halogen, —N 3 , —CF 3 , —CCl 3 , —CBr 3 , —CI 3 , —CN, —CHO, —OR 33H , —NR 34H R 35H , —COOR 33H , —CONR 34H R 35H , —NO 2 , —SR 36H , —SO n8 R 34H , —SO n8 OR 34H , —SO n8 NR 34H R 35H , —NHNR 34H R 35H , —ONR 34H R 35H , —NHC(O)NHNR 34H R 35H , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
R 33A , R 34A , R 35A , R 36A , R 33B , R 34B , R 35B , R 36B , R 33C , R 34C , R 35C , R 36C , R 33D , R 34D , R 35D , R 36D , R 33E , R 34E , R 35E , R 36E , R 33F , R 34F , R 35F , R 36F , R 33G , R 34G , R 35G , R 36G , R 33H , R 34H , R 35H , and R 36H are independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; and
n1, n2, n3, n4, n5, n6, n7, and n8 are independently 1 or 2.

2. The method of claim 1 , wherein the ring bridging trisulfide compound is:

and the ring bridging disulfide compound is:

wherein:
X 3 is N or CR 7 ;
X 4 is N or CR 8 ;
X 5 is N or CR 9 ;
R 7 is hydrogen, halogen, —N 3 , —CF 3 , —CCl 3 , —CBr 3 , —CI 3 , —CN, —CHO, —OR 33I , —NR 34I R 35I , COOR 33I , —CONR 34I R 35I , —NO 2 , —SR 36I , —SO n9 R 34I , —SO n9 OR 34I , —SO n9 NR 34I R 35I , —NHNR 34I R 35I , —ONR 34I R 35I , —NHC(O)NHNR 35I R 34I , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
R 8 is hydrogen, halogen, —N 3 , —CF 3 , —CCl 3 , —CBr 3 , —CI 3 , —CN, —CHO, —OR 33J , —NR 34J R 35J , —COOR 33J , —CONR 34J R 35J , —NO 2 , —SR 36J , —SO n10 R 34J , —SO n10 OR 34J , —SO n10 NR 34J R 35J , —NHNR 34J R 35J , —ONR 34J R 35J , —NHC(O)NHNR 34J R 35J , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
R 9 is hydrogen, halogen, —N 3 , —CF 3 , —CCl 3 , —CBr 3 , —CI 3 , —CN, —CHO, —OR 33K , —NR 34K R 35K , —COOR 33K , —CONR 34K R 35K , —NO 2 , —SR 36K , —SO n11 R 34K , —SO n11 OR 34K , —SO n11 NR 34K R 35K , —NHNR 34K R 35K , —ONR 34K R 35K , —NHC(O)NHNR 34K R 35K , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
R 10 and R 11 are independently hydrogen, halogen, —N 3 , —CF 3 , —CCl 3 , —CBr 3 , —CI 3 , —CN, —CHO, —OR 33L , —NR 34L R 35L , —COOR 33L , —CONR 34L R 35L , —NO 2 , —SR 36L , —SO n12 R 34L , —SO n12 OR 34L , —SO n12 NR 34L R 35L , —NHNR 34L R 35L , —ONR 34L R 35L , —NHC(O)NHNR 34L R 35L , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or u

Assignees

• Hope City

Inventors

• Horne David
• Xie Jun

Classifications

• C07C319/00

  Preparation of thiols, sulfides, hydropolysulfides or polysulfides · CPC title

• C07D513/18 Primary

  Bridged systems · CPC title

• C07C319/14

  of sulfides · CPC title

• C07C319/20

  by reactions not involving the formation of sulfide groups · CPC title