反应详情

48 (1.2 eq.) and HATU (1.2 eq.) were added to a 0.12M solution of (9R,11S,14S,20E)-14-cyclohexyl-13-oxo-8-oxa-12,15-diazatetracyclo[20.3.1.12,6.19,12]octacosa-1(26),2(28),3,5,20,22,24-heptaene-11-carboxylic acid 111 in DMF containing DIPEA (4.0 eq.). The reaction mixture was stirred at RT overnight then it was concentrated to dryness and the residue was dissolved in DMSO and purified by RP-HPLC (stationary phase: column WATERSXBRIDGE 19×150 mm, 5 μm; mobile phase: MeCN/H2O buffered with 0.1% TFA from 50% to 90% of MeCN in 14 min., run time 18 min.). Fractions containing the pure compound were combined and freeze dried to afford compound 146 (TFA salt) as an off white solid (4.0% over 3 steps). 1H NMR (400 MHz, DMSO-d6, 300 K) δ 10.73 (s, 1H), 8.83 (s, 1H), 8.80-8.68 (m, 1H), 8.58-8.42 (m, 1H), 7.92 (s, 2H), 7.68 (d, J 7.6, 1H), 7.62 (d, J 7.6, 1H), 7.51-7.40 (m, 2H), 7.29 (t, J 8.1, 2H), 6.58 (d, J 15.7, 1H), 6.49-6.37 (m, 1H), 5.68-5.54 (m, 1H), 5.27 (d, J 16.9, 1H), 5.16 (d, J 11.6, 1H), 4.74 (d, J 11.9, 1H), 4.60 (d, J 11.9, 1H), 4.50-4.33 (m, 3H), 4.19 (d, J 11.1, 1H), 3.86 (dd, J 11.1, 3.8, 1H), 3.18-2.91 (m, 3H), 2.60-2.46 (m, partially obscured by residual DMSO-d6, 1H), 2.43-2.24 (m, 2H), 2.19 (q, J 8.8, 1H), 2.09-1.97 (m, 1H), 1.92-1.65 (m, 9H), 1.64-1.52 (m, 1H), 1.38-1.02 (m, 11H). MS (ES) m/z 729 (M+H)+.

1. concentrationit was concentrated to dryness
2. dissolutionthe residue was dissolved in DMSO
3. custompurified by RP-HPLC (stationary phase: column WATERSXBRIDGE 19×150 mm, 5 μm; mobile phase: MeCN/H2O buffered with 0.1% TFA from 50% to 90% of MeCN in 14 min., run time 18 min.)
4. additionFractions containing the pure compound
5. customfreeze dried