1,4-Dioxane → 4-Cyano-3-[5-methoxy-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrrolo[2,3-c]pyridin-4-yl]-benzoic acid methyl ester

Participants

Reaction Conditions

Reaction Steps

A mixture of 4-Bromo-5-methoxy-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrrolo[2,3-c]pyridine (0.940 g, 2.63 mmol), 4-Cyano-3-(4,4,5,5-tetramethyl-[1,3,2]dioxa-borolan-2-yl)-benzoic acid methyl ester (Example 140 Step 1 starting material) (0.840 g, 2.93 mmol, 1.1 eq), Bis(di-tertbutyl-(4-dimethylaminophenyl)-phosphine)-di-chloropalladium (II) (0.046 g, 0.066 mmol, 2 mol %), and tribasic potassium phosphate (1.12 g, 5.26 mmol, 2 eq) in a 10:1 mixture of dioxane and water was heated to 80° C. for 2.5 hr. The reaction was cooled to 23° C., the contents decanted into a separatory funnel and the residue in the vial was washed with copious amounts of ethyl acetate. The organic was washed with water, brine, dried (Na2SO4), and concentrated. The crude mixture was further purified by chromatography eluting with 30% EtOAc/Heptane giving 4-Cyano-3-[5-methoxy-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrrolo[2,3-c]pyridin-4-yl]-benzoic acid methyl ester as a yellow amorphous solid (0.790 g, 1.81 mmol, 69%). MS ESI m/z 438.4 (M+H)+. 1NMR (400 MHz, CDCl3) δ 8.59 (s, 1H), 8.27 (d, J=1.6 Hz, 1H), 8.12 (dd, J=8.0 Hz, 1.6 Hz, 1H), 7.90 (d, J=8.0 Hz, 1H), 7.33 (d, J=3.2 Hz, 1H), 6.20 (d, J=3.2 Hz, 1H), 5.54 (d, J=5.0 Hz, 2H), 4.04 (s, 3H), 3.98 (s, 3H), 3.55 (m, 2H), 0.95 (m, 2H), 0.00 (s, 9H).

Provenance & Evidence