Reacción #1955490

Ecuación de reacción

K2CO3

17

4-amino-2-bromo-thieno[3,2-c]pyridine-7-carboxylic acid amide

5-bromo-1,3-dihydro-benzo[c]thiophene 2,2-dioxide

bis(pinacolato)diboron

KOAc

→

68

4-Amino-2-(2,2-dioxo-2,3,3a,7a-tetrahydro-1H-2λ6-benzo[c]thiophen-5-yl)-thieno[3,2-c]pyridine-7-carboxylic acid amide

Disolventes

DMSO

H2O

DMSO

Condiciones de reacción

Tratamiento posterior

1. 1
   OtroThe mixture was degassed with N2
2. 2
   Filtraciónthen filtered
3. 3
   LavadoThe residue was washed with DMSO (2 mL)
4. 4
   Otrothe filtrate purified by reverse phase preparative HPLC

Procedimiento

To a stirred solution 5-bromo-1,3-dihydro-benzo[c]thiophene 2,2-dioxide (160 mg, 0.65 mmol) 67 (Salor, Milwaukee, Wis.) in DMSO (1 mL) was added bis(pinacolato)diboron (178 mg, 0.70 mmol), KOAc (159 mg, 1.6 mmol) and Pd(dppf)Cl2 DCM complex (22 mg, 0.027 mmol). The mixture was degassed with N2 and heated at 85° C. for 2 h then DMSO (2 mL), H2O (0.5 mL), K2CO3 (223 mg, 1.6 mmol) and 4-amino-2-bromo-thieno[3,2-c]pyridine-7-carboxylic acid amide H2SO4 salt 17 (200 mg, 0.54 mmol) were added. The mixture was stirred at 85° C. for a further 12 h then filtered. The residue was washed with DMSO (2 mL) and the filtrate purified by reverse phase preparative HPLC to yield 68 as a white solid. 1H-NMR (400 MHz, d6-DMSO) δ 8.31 (s, 1H), 8.24 (s, 1H), 8,19 (bs, 1H), 7.97-7.92 (m, 3H), 7.85 (d, 1H), 4.78 (s, 2H), 4.71 (s, 2H).

Fuente