HCID 59605344, compound → HCID 59605437, compound

Participants

Reaction Steps

A 25 mL round-bottomed flask, under nitrogen, fitted with a condenser/inert gas bubbler (via a Claisen head), was charged with a solution of 2-{4-[2-(1-benzenesulfonyl-2-methyl-1H-pyrrolo[2,3-c]pyridin-4-yl)-4-morpholin-4-yl-thieno[3,2-d]pyrimidin-6-ylmethyl]piperazine-1-yl}isobutyramide (0.17 g, 0.25 mmol) in dioxane (4 mL), IMS (4 mL) and NaOH 12.5M (0.4 mL). The resulting mixture was stirred at room temperature for 2.5 h. The solution was concentrated in vacuo, the residue diluted with MeOH and loaded onto a Isolute® SCX-2 cartridge treated with MeOH. The cartridge was washed with MeOH (100 mL) and the product was recovered eluting with 2N NH3 in MeOH, the eluent concentrated, suspended in dioxane/water and freeze-dried overnight. The resultant solid was dissolved in DMSO and purified by preparative HPLC (C18 column) gradient: (acetonitrile/20 mM triethylamine) 10% to 98% in (water/20 mM triethylamine) over 20 min (flow rate 18 ml/min). The product was freeze-dried overnight yielding 142 as a white powder (0.047 g, 35%). LCMS (Method E): RT=5.27 min, [M+H]+ 535.2. 1H NMR (DMSO, 400 MHz): δ 11.43 (s, 1 H); 8.22 (d, J=5.4 Hz, 1 H); 7.43 (s, 1 H); 7.33 (dd, J=6.3, 0.9 Hz, 1 H); 7.07 (d, J=3.5 Hz, 1 H); 6.95 (d, J=3.45 Hz, 1 H); 6.87 (s, 1 H); 3.98 (t, J=4.6 Hz, 4 H); 3.87 (s, 2 H); 3.81 (t, J=4.6 Hz, 4 H); 3.57 (s, 3 H); 2.61-2.53 (m, 2 H); 2.49-2.45 (m, 2 H); 2.44 (s, 4 H); 1.08 (s, 6 H)

Provenance & Evidence