1,4-Dioxane → (2S,4S)-4-[4-(6-Amino-5-benzothiazol-2-ylpyridin-3-yl)-pyrazol-1-yl]-pyrrolidine-2-carboxylic acid

Participants

Reaction Conditions

Reaction Steps

A mixture of 3-benzothiazol-2-yl-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-pyridin-2-ylamine (BB8) (200 mg, 0.566 mmol), (2S,4S)-4-(4-iodopyrazol-1-yl)-pyrrolidine-1,2-dicarboxylic acid 1-benzyl ester 2-methyl ester (309.0 mg, 0.679 mmol), Pd(PPh3)4 (60 mg, 0.06 mmol), potassium fluoride (98.7 mg, 1.70 mmol), and 4:1 dioxane:water (5 mL) was heated in the microwave reactor at 85° C. for 30 min. The material was concentrated in vacuo, then dry-loaded onto silica gel for column chromatography. The product was eluted with 2→5% MeOH/DCM, and the fractions containing the product were concentrated in vacuo. The material was dissolved in conc. HCl, transferred to a sealed tube and heated at 60° C. for 2 h. The solvent was removed using the corrosive pump to afford the title compound as a brown solid. 1H NMR (400 MHz, CD3OD): δ=2.73 (ddd, J=14.0, 6.5, 4.5 Hz, 1H), 3.07 (ddd, J=14.1, 10.0, 7.5 Hz, 1H), 3.81-3.93 (m, 2H), 4.68 (dd, J=10.0, 6.7 Hz, 1H), 5.36 (ddd, J=6.8, 3.8, 3.5 Hz, 1H), 7.56-7.63 (m, 2H), 8.05 (s, 1H), 8.08-8.11 (m, 1H), 8.16 (d, J=7.6 Hz, 1H), 8.32-8.36 (m, 2H), 8.72 (d, J=2.0 Hz, 1H). MS (ES′): m/z=407.13 (100) [MH+]. HPLC: tR=2.28 min (ZQ2, polar—5 min).

Provenance & Evidence