Hydrochloric Acid → Des-6-[4-(2-hydroxyethyl)-1-piperazinyl]-6-chloro-O-pivalate Dasatinib

Participants

Reaction Conditions

Reaction Steps

To a solution of compound 10a (2.21 g, 6 mmol) and 4,6-dichloro-2-methylpyrimidine (11a, 1.18 g, 7.2 mmol) in THF (30 mL) was added a solution of NaOBu-t in THF (30% w/w, 7.4 mL) at temperature between 10° C. to 18° C. The reaction mixture was stirred at 18° C. for 1.5 h. It was then cooled to 0° C. A solution of 1N HCl (14.0 mL) was added. The mixture then was partitioned between EtOAc and H2O (1:1, 200 mL). The organic phase was separated, and the aqueous layer was extracted with EtOAc (100 mL). The combined extracts were concentrated in vacuo. The residue was subjected to a flash column using 50% EtOAc in hexane to give crude compound 12a which was triturated with 10% EtOAc in hexane to give compound 12a (1.95 g, 66% yield). 1H NMR (500 MHz, CDCl3) δ 1.19 (s, 9H), 2.73 (s, 3H), 5.12 (s, 2H), 6.93 (s, 1H), 7.21-7.49 (m, 3H), 8.21 (s, 1H), 8.98 (s, 1H).

Provenance & Evidence