Synthesis of PHA‐690509 labelled with ¹⁴C

Abstract

PHA-690509, a cyclin-dependent kinase A inhibitor, has been labelled with carbon-14. [ 14 C]PHA-690509 was obtained via a three-step procedure in 10% overall radiochemical yield starting from [ 14 C]thiourea 3.

3,5,7-Substituted Pyrazolo[4,3-d]pyrimidine Inhibitors of Cyclin-Dependent Kinases and Their Evaluation in Lymphoma Models

“…The precursor 2-bromo-3-methyl-1-butanol was prepared from 3-methylbutenal by bromination with a bromine–dioxane complex (1:1) according to the literature . The obtained 2-bromo-3-methylbutanal was then reduced to the desired 2-bromo-3-methyl-1-butanol in the usual manner using NaBH 4 and was used for alkylation without purification.…”

“…The product was purified stepwise ( The precursor 2-bromo-3-methyl-1-butanol was prepared from 3methylbutenal by bromination with a bromine−dioxane complex (1:1) according to the literature. 45 The obtained 2-bromo-3methylbutanal was then reduced to the desired 2-bromo-3-methyl-1-butanol in the usual manner using NaBH 4 and was used for alkylation without purification. 46 ) was added dropwise at room temperature to a stirred mixture of 3-isopropyl-7-[4-(2-pyridyl)benzyl]amino-1(2)Hpyrazolo [4,3-d]pyrimidine-5-thiol 3 (0.38 g, 1.0 mmol) and 1 mL of aq 48% HBr solution in DMF (10 mL).…”

Discovery of Imidazo[2,1-b]thiazole HCV NS4B Inhibitors Exhibiting Synergistic Effect with Other Direct-Acting Antiviral Agents

“…Starting from the common substrate 4-methylpentan-2-one, compound 8d and 8g were prepared after two collective steps with a ratio of 1:7 due to lack of chemoselectivity for bromination. For the synthesis of 5-isopropylthiazol-2-amine 8c , bromination and cyclization were completed in one pot due to the instability of 2-bromo-3-methylbutyraldehyde under room temperature . Cyclization of various 2-aminothiazoles 8a – g with ethyl bromopyruvate followed by chlorination of the resultant intermediates 9a – g furnished imidazo[2,1- b ]thiazole-6-carboxylic acid esters 10a – i , which went through LiOH-mediated ester hydrolysis to produce carboxylic acids 11a – i ( Scheme ) .…”