5-Chloro-1,2,4-thiadiazole

A solution of dry MeCN (226 mg, 11 mmol) in dry THF (25 ml) was added LiHIVIDS (5.5 mmol, 5.5 mL) at 0 °C, then the mixture was stirred at 0 °C for 30 mi 5-chloro-1, 2, 4- thiadiazole (691 mg, 5.5 mmol) in dry THF (5 mL) was added to the mixture at 0 °C, then stirred at rt overnight. The reaction mixture was quenched by H20 (1 mL), and extracted by EA (30 mL X 3), dried with Na2SO4, filtered and dried in vacuo to afford the crude product. Further purification by column chromatography (Si02, 100 g, 200-3 00 m, eluted by PE/EA = 5:1) gave the desired product (410 mg, 60percent) as yellow solid. MS [M+H] calcd for C4H3N35126.0, found 126.0.Parallel preparation of Examples 145-148: To a set of vials individually containing requisite aryl chloride or bromide (0.063 mmol) and Cs2C03 (51 mg, 0.16 mmol) was added a solution of the piperazine from Scheme C (25 mg, 0.052 mmol) in THF (1 mL). The vials were capped and transferred to a glove box under an atmosphere of nitrogen. To each vial was added chloro(2-dicyclohexylphosphino-2', 6'-di-i-propoxy-l, l '- biphenyl)[2-(2-aminoethylphenyl)]palladium(II), methyl-t-butylether adduct (Strem) (2.1 mg, 0.0026 mmol). The vials were capped and heated at 80°C overnight. The vials were cooled to RT and removed from the glove box. To each vial was added water. The mixtures were extracted with CH2C12 and the organic layers were transferred into a new set of vials. The organic layers were dried in vacuo. To each vial was then added THF:MeOH (1 :3, 1 mL) followed by HC1 (4 N in dioxane, 0.20 mL, 0.80 mmol). The vials were capped and the solutions were heated to 70°C for 0.5 h. The solutions were allowed to cool to RT and the solvent was then removed in vacuo. Each crude product was redissolved in 1 mL of DMSO and filtered. The crude products were purified by mass triggered HPLC. Examples 145-146 were purified using the following conditions: [Waters Sunfire C18 column, 5muetaiota, 19x100 mm, gradient 10percent to 60percent MeCN (0.1percent formic acid) in water (0.1 percent formic acid) 50 mL/min, 8 min run time] Examples 147-148 were purified using the following conditions: [Waters XBridge CI 8 column, 5muiotaeta, 19x100 mm, gradient ranges from 10percent initial to 70-76percent MeCN (0.1percent NH4OH) in water (0.1percent NH4OH) 50 mL/min, 8 min run time].

Molecular Weight:120.56
XLogP3:1.7
Hydrogen Bond Acceptor Count:3
Exact Mass:119.9548969
Monoisotopic Mass:119.9548969
Topological Polar Surface Area:54
Heavy Atom Count:6
Complexity:50.8
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes