1H-BenziMidazole-1-carboxylic acid, 6-Methyl-5-(4,4,5,5-tetraMethyl-1,3,2-dioxaborolan-2-yl)-, 1,1-diMethylethyl ester synthesis

Yield:-

Reaction Conditions:

with potassium phosphate;DavePhos;palladium diacetate in toluene at 95; for 18 h;

Steps:

30.b Example 30; 4-[3-(6-Methyl-3H-benzoimidazol-5-yl)-benzenesulfonyl]-5-methylsulfanyl- thiophene-2-carboxayrzidine bis-trifluoroacetate; b); 5-Methyl-6-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzoimidazole-1-carboxylic acid tert-butyl ester and 5-methyl-6-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzoimidazole-1-carboxylic acid tert- butyl ester

To a dry reaction vial fitted with a stir bar and a TEFLON#-LINED screw cap, a mixture of 5-chloro-6-methyl-benzoimidazole-1-carboxylic acid tert- butyl ester and 5-CHLORO-6-METHYL-BENZOIMIDAZOLE-3-CARBOXYLIC acid tert-butyl ester (150 mg, 0.56 mmol, as prepared in Example 30, step a), 4,4,5,5,4',4',5',5'-octamethyl-[2, 2']bi[[1,3,2]dioxaborolanyl] (284 mg, 1.12 mmol, Aldrich Chemical Company), (2'-dicyclohexylphosphanyl-biphenyl-2-yl)-dimethyl-amine (17.7 mg, 0.045 mmol, Strem Chemicals Inc, Newburyport, MA), Pd (OAC) 2 (6.7 mg, 0.03 mmol. Strem Chemicals Inc, Newburyport, MA), and K3PO4 (238 mg, 1.12, mmol) were added. The vial was capped, purged with argon, and then suspended in toluene (3 mL). After stirring for 18 hr at 95 oC, the reaction was allowed to cool and then filtered through Celite. # The filtrate was concentrated in vacuo and the residue was purified using preparative thin layer chromatography (1: 3 EtOAc/hexanes, 2000 A SI02 plate) to afford 100 mg (50%) of the title compound (1: 1 mixture of regioisomers) as a yellow oil. ESI-MS (m/z): Calcd. for CL9H27BN204 : 358.2 ; found: 303.2 (M-tBu), 259.3 (M-Boc).

References:

WO2003/99805,2003,A1 Location in patent:Page 123