Sodium Bicarbonate → 1-[5-(4-Aminothieno[3,2-C]pyridin-3-Yl)-2,3-Dihydro-1h-Indol-1-Yl]-2-Phenylethanone

Participants

Reaction Conditions

Reaction Steps

In a sealed tube, to 5-bromo-1-(phenylacetyl)-2,3-dihydro-1H-indole (0.658 g, 2.081 mmol), bispinacolatodiboron (0.634 g, 2.497 mmol) and potassium acetate (0.613 g, 6.24 mmol) was added 1,4-Dioxane (15 mL) and the mixture was degassed with N2 for 10 minutes. PdCl2(dppf)-CH2Cl2 Adduct (0.085 g, 0.104 mmol) was added and the reaction mixture was stirred for 48 hours at 100° C. The mixture was cooled to room temperature and treated with 5 mL of water, 3-bromothieno[3,2-c]pyridin-4-amine (0.524 g, 2.289 mmol) and NaHCO3 (175 mg). The mixture was degassed with N2 for 10 minutes. PdCl2(dppf)-CH2Cl2 Adduct (0.085 g, 0.104 mmol) was added and the reaction mixture was stirred overnight at 100° C. The mixture was poured onto water and ethyl acetate, then filtered. The filtrate was poured into a separatory funnel. The organic layer was separated and the aqueous layer was further extracted with ethyl acetate. The combined organic layers were washed with brine, dried (MgSO4), filtered and concentrated. Flash chromatography on SiO2 (gradient: 100% CHCl3 to 90:10:1 CHCl3/CH3OH/NH4OH) afforded a few fractions containing the desired product with impurity. The fractions were combined and evaporated. To the resulting residue was dissolved in MeOH/CH2Cl2 (1 mL/5 mL). Then dry loaded and purified by Analogix silica 25/14, gradient 0-100% EtOAc/hexane. The compound came out at 95% EtOAc. The fractions with the pure compound were combined. The solvents were evaporated and the resulting residue was triturated in EtOAc to give off-white solid (280 mg) of the title compound 3-[1-(phenylacetyl)-2,3-dihydro-1H-indol-5-yl]thieno[3,2-c]pyridin-4-amine. LC-MS (ES) m/z=386.0 [M+H]+. 1H NMR (400 MHz, DMSO-d6) δ ppm 8.16 (d, J=8.3 Hz, 1H) 7.82 (d, J=5.6 Hz, 1H) 7.41 (s, 1H) 7.19-7.38 (m, 8H) 5.41 (br. s., 2H) 4.25 (t, J=8.6 Hz, 2H) 3.89 (s, 2H) 3.23 (t, 2H).

Provenance & Evidence