EDTA disodium salt → 1,1-Dioxo-tetrahydro-thiopyran-4-one

To a solution of tetrahydrothiopyran-4-one (400 mg) stirring in acetonitrile (5 ml) and Na2.EDTA (0.0004 M aq, 3 ml) was added potassium peroxymonosulphate (Oxone, 6.34 g) and NaHCO3 (2.69 g) in several aliquots over 30 minutes. The reaction mixture was stirred at room temperature for a further 2 hours, then diluted with water (40 ml), extracted into dichloromethane, and dried (MgSO4) to give 1,1-dioxo-tetrahydro-thiopyran-4-one (330 mg) as a white solid. To this compound (75 mg) stirring in anhydrous 1,2-dichloroethane (6 ml) was added 2-chloro-4-morpholin-4-yl-thienopyrimidine-6-yl methyl methylamine (150 mg, as previously prepared from 2-chloro-4-morpholin-4-yl-thienopyrimidine-6-carbaldehyde and methylamine under reductive amination conditions), followed by glacial acetic acid (31 μl) and sodium triacetoxy borohydride (138 mg). The reaction mixture was stirred for 24 hours at room temperature, and the product isolated by extraction into dichloromethane, followed by purification by flash chromatography to give (2-chloro-4-morpholin-4-yl-thienopyrimidine-6-ylmethyl)-(1,1-dioxo-hexahydro-thiopyran-4-yl)-methyl-amine (115 mg) as a yellow solid, which was used in a Suzuki coupling with 4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-indazole, to give, after flash silica purification the title compound (38 mg) as a white solid.

1. extractionextracted into dichloromethane
2. dry with materialdried (MgSO4)

ORD record

ord-cbe9d330438a4e22a978c024ac153063

Source dataset

uspto-grants-2014_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08802670B2