Tetrahydrofuran → N-(5-Bromo-pyridin-2-yl)-3-(7-isopropyl-pyrido[2,3-d]pyrimidin-4-ylamino)-4-{4-[3-((R)-1-phenyl-ethyl)-ureido]-phenylsulfanyl}-benzamide

Participants

Reaction Conditions

Reaction Steps

The product of Example 364E (152 mg, 0.2 mmol) in tetrahydrofuran (2 mL) was treated with 1,8-diazobicyclo[5.4.0]undec-7-ene (60 μL, 0.4 mm01) and (R)-(+)-α-methylbenzylamine (121 mg, 1.0 mmol) and heated at 60° C. for 1 hour in a sealed tube. The reaction mixture was cooled, concentrated and the residue was purified by preparative HPLC on a Waters Symmetry C8 column (40 mm×100 mm, 7 um particle size) using a gradient of 10% to 100% acetonitrile: aqueous ammonium acetate (10 mM) over 12 min (15 min run time) at a flow rate of 70 mL/min to give the title compound (21 mg, 14%). 1H NMR (300 MHz, DMSO-D6) δ ppm: 1.33 (d, J=6.99 Hz, 6 H) 1.40 (d, J=6.62 Hz, 3 H) 3.22 (m, 1 H) 4.82 (m, 1 H) 6.73 (d, J=8.09 Hz, 1 H) 6.90 (s, br, 1 H) 7.24 (m, 1 H) 7.35 (m, 6 H) 7.48 (m, 2 H) 7.63 (s, br, 1 H) 7.86 (s, br, 1 H) 8.04 (d, J=2.57 Hz, 1 H) 8.07 (d, J=2.57 Hz, 1 H) 8.17 (m, 1 H) 8.49 (d, J=2.57 Hz, 1 H) 8.60 (s, 1 H) 8.66 (s, 1 H) 8.86 (s, br, 1 H) 10.28 (s, 1 H) 10.95 (s, 1 H); (ESI+) m/z 733 735 (M+H)+.

Provenance & Evidence