Diisopropylethylamine → HCID 131731691, compound

Participants

Reaction Conditions

Reaction Steps

To a 100 ml flask were added (S)-2-(3-(2-amino-3-(4-chlorophenyl)propanamido)-5-(pyridin-4-yl)phenyl)-2-methylpropanoic acid TFA salt 63.1.C (200 mg, 0.36 mmole), thiazole-4-carbaldehyde (33 mg, 0.21 mmole), sodium triacetoxyborohydride (154 mg, 0.73 mmole), 20 ml of DCE, 1 ml MeOH and DIEA (95 μl, 0.54 mmole). The reaction was stirred at 70° C. for 2 hours at which time sodium cyanotrihydroborate (46 mg, 0.73 mmole) was added and stirred at 70° C. for an additional 1 hour. The reaction mixture was then partitioned between CH2Cl2 and water and the solvent was removed from the organic layer by rotary evaporation. The crude product was purified by reverse phase preparative HPLC to give (S)-2-(3-(3-(4-chlorophenyl)-2-(thiazol-4-ylmethylamino)propanamido)-5-(pyridin-4-yl)phenyl)-2-methylpropanoic acid TFA salt 63.1 as an off white solid (72.5 mg, 60% yield). LCMS ESI (pos.) m/e: 535.2 (M+1): 1H NMR (500 MHz, MeOH) δ ppm 9.14 (d, J=1.96 Hz, 1H), 8.79-8.91 (m, 2H), 8.14-8.25 (m, 2H), 7.99 (t, J=1.71 Hz, 1H), 7.82 (d, J=1.96 Hz, 1H), 7.69 (t, J=1.59 Hz, 1H), 7.52 (t, J=1.71 Hz, 1H), 7.35 (m, 2H), 7.27 (m, 2H), 4.43-4.63 (m, 2H), 4.28 (dd, J=9.29, 5.87 Hz, 1H), 3.45 (dd, J=13.45, 5.62 Hz, 1H), 3.24 (dd, J=13.33, 9.41 Hz, 1H), 1.65 (d, J=6.85 Hz, 6H).

Provenance & Evidence