Amino-thienopyrimidine Series

Synthesis of Boronic Acid Pinacol Ester - MNR103-1 was repeated at a scale of 0.7067. 3-bromobenzenesulfonamide (1.06 g, 4.488 mmol), bis(pinacolato)diboron (1.710 g, 6.735 mmol), potassium acetate (1.762 g, 17.96 mmol) was dissolved in 1,4-dioxan (22.5 mL) and degassed with argon for ten minutes. Pd(dppf)2.CH2Cl2 [1] (184 mg, 0.226 mmol) was added and the reaction heated to reflux under argon for 22 hours, then cooled and filtered through a plug of celite, followed by washings with methanol (20 ml) and dichloromethane (20 ml). The combined organic layers were concentrated in vacuo and purified using dry column vacuum chromatography (1-10% methanol in dichloromethane, 10 fractions) to give three products:

C1, a tan solid (380 mg)

NMR indicated only one set of aromatic peaks consistent with the desired product and some excess pinacol. This was triturated overnight in hexanes (25 mL) and filtered to give a pale cream solid D1(171 mg). NMR indicated that all residual pinacol had been removed. 

C2, a dark oily solid (1.773 g)

NMR indicated only one set of aromatic peaks consistent with the desired product and a large amount of excess pinacol. This was recrystallised from ethanol/water (1:1) to give grey crystals D2 (305 mg). NMR indicated that all residual pinacol had been removed. 

C3, a tan solid (49 mg)

NMR indicated only one set of aromatic peaks consistent with the desired product and a small amount of excess pinacol.

InChi String:

InChI=1S/C6H6BrNO2S/c7-5-2-1-3-6(4-5)11(8,9)10/h1-4H,(H2,8,9,10)

and

InChI=1S/C12H24B2O4/c1-9(2)10(3,4)16-13(15-9)14-17-11(5,6)12(7,8)18-14/h1-8H3

gives

InChI=1S/C12H18BNO4S/c1-11(2)12(3,4)18-13(17-11)9-6-5-7-10(8-9)19(14,15)16/h5-8H,1-4H3,(H2,14,15,16)

Notes:

1) used instead of Pd(dppf)2Cl2 due to availability of dichloromethane complex;