Diisopropylethylamine → [3-cyclopropyl-5-fluoro-2-[(1S)-1-(thiazolo[5,4-d]pyrimidin-7-ylamino)ethyl]benzimidazol-4-yl]-morpholino-methanone

Participants

Reaction Conditions

Reaction Steps

A mixture of [2-((S)-1-aminoethyl)-3-cyclopropyl-5-fluoro-3H-benzoimidazol-4-yl]-morpholin-4-yl-methanone (108 mg, 0.33 mmol), 7-chloro-thiazolo[5,4-d]pyrimidine (61 mg, 0.36 mmol) and DIPEA (170 μL, 0.98 mmol) in IPA (1 mL) was heated at 90° C. in a sealed vial for 17 h. After cooling to RT, the reaction mixture was diluted with MeOH and loaded onto an Isolute® SCX-2 cartridge. The cartridge was washed with MeOH followed by 2M NH3/MeOH. The basic fractions were combined, concentrated in vacuo and the resulting residue purified by column chromatography (Si—PCC, gradient 0-10% MeOH in DCM) to afford 400 as a pale yellow solid (110 mg, 39%). LCMS (Method K): RT 3.16 min [M+H]+ 468.02. 1H NMR (CDCl3, 400 MHz): δ 8.82 (0.7H, s), 8.77 (0.3H, s), 8.54 (0.3H, s), 8.52 (0.7H, s), 7.73-7.65 (1H, m), 7.17 (0.7H, d, J=8.02 Hz), 7.05-6.95 (1H, m), 6.67 (0.3H, d, J=8.45 Hz), 6.31-6.23 (0.3H, m), 6.14-6.04 (0.7H, m), 4.23-4.14 (1H, m), 3.93-3.72 (4H, m), 3.68-3.51 (2H, m), 3.47-3.33 (2H, m), 1.84 (1H, d, J=6.77 Hz), 1.75 (2H, d, J=6.76 Hz), 1.54-1.46 (0.7H, m), 1.41-1.29 (1H, m), 1.20-1.10 (0.3H, m), 1.03-0.93 (1H, m), 0.86-0.71 (1H, m)

Provenance & Evidence