Solid-Phase Synthesis of 2-Amino-5-sulfanylthiazoles

Abstract

A solid-phase synthesis that provides easy access to 2-amino-5-sulfanylthiazoles with variable substituents at C-2, C-4, and C-5 has been developed. The key step of this synthesis is a new C-sulfanylation of resin-bound 2-aminothiazoles by mixtures of various sulfur-containing building blocks and iodine. The resulting 2-amino-5-sulfanylthiazoles were obtained in high purities and yields after cleavage from the

Human Glucagon Receptor Antagonists with Thiazole Cores. A Novel Series with Superior Pharmacokinetic Properties

“…Commercially available Fmoc-β-Ala-Wang resin was deprotected and coupled with 4-formylbenzoic acid using HOBt/DIC activation. The amine was prepared through reductive amination of the aldehyde functionality, and the benzylic amine was subsequently treated with Fmoc-NCS. , Deprotection, reaction with α-bromoketones, and cleavage from the resin furnished the desired products in both high yields and good purities. By use of this procedure, several focused libraries comprising more than 800 analogues were prepared.…”

One-Pot, Three-Component Synthesis of 5-Sulfenyl-2-iminothiazolines by Cross-Dehydrogenative C–S Coupling Using I2/DMSO in Open Air

“…al. reported the solid-phase synthesis of 2-amino-5-sulfanylthiazoles, which involves C–S bond formation . Subsequently, several transition-metal-free methodologies have been explored using a variety of sulfenylation reagents such as arylsulfonyl chlorides, diaryldisulfides, sulfonyl hydrazides, and sulfinic acids .…”

“…al. reported the solid-phase synthesis of 2-amino-5-sulfanylthiazoles, which involves C−S bond formation. 10 Subsequently, several transition-metal-free methodologies have been explored using a variety of sulfenylation reagents such as arylsulfonyl chlorides, 11 diaryldisulfides, 12 sulfonyl hydrazides, 7e and sulfinic acids. 13 In addition, a variety of catalytic systems such as Nbromosuccinimide (NBS), 14 I 2 /dimethyl sulfoxide (DMSO), 3d,15 N-chlorosuccinimide (NCS), 7d,16 I 2 /H 2 O 2 , 17 (NH 4 ) 2 S 2 O 8 , 18 copper catalysts, 19 hypervalent iodine reagents, 20 and Pd/Al 2 O 3 /CuCl 2 21 have been explored for C− S bond formation through the C−H functionalization strategy.…”

Generation of Drug‐Like Five‐Membered Heterocyclic Libraries Using Carbon Disulfide and Merrifield Resin

“…17 The solution-phase synthesis of 3-alkyldithiocarbonyloxazolidines 18 and 5-thia-1,3,8-triaza-cyclopenta[b]naphthalen-7-ones 19 was developed by using carbon disulfide as a substituted site. 22 In addition, some research groups established the synthesis of 2-amino-5-sulfanylthiazoles using isothiocyanate as a sulfur source, 23 and the synthesis of 1,3,4-thiadiazoles using DPTas a sulfur source, 24 or using isothiocyanate as a sulfur source and diversity element 25 on a solid support. 22 In addition, some research groups established the synthesis of 2-amino-5-sulfanylthiazoles using isothiocyanate as a sulfur source, 23 and the synthesis of 1,3,4-thiadiazoles using DPTas a sulfur source, 24 or using isothiocyanate as a sulfur source and diversity element 25 on a solid support.…”