Trifluoroacetic acid → N-(2,3-dihydroxypropyl)-5-(5-phenyl-4-((pyridin-2-ylmethyl)amino)phthalazin-1-yl)nicotinamide
Reaction equation
CC1(C)[O:6][CH:5]([CH2:7][NH:8][C:9](=[O:40])[C:10]2[CH:15]=[C:14]([C:16]3[C:25]4[C:20](=[C:21]([C:26]5[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=5)[CH:22]=[CH:23][CH:24]=4)[C:19]([NH:32][CH2:33][C:34]4[CH:39]=[CH:38][CH:37]=[CH:36][N:35]=4)=[N:18][N:17]=3)[CH:13]=[N:12][CH:11]=2)[CH2:4][O:3]1.C(O)(C(F)(F)F)=O>>[OH:6][CH:5]([CH2:4][OH:3])[CH2:7][NH:8][C:9](=[O:40])[C:10]1[CH:15]=[C:14]([C:16]2[C:25]3[C:20](=[C:21]([C:26]4[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=4)[CH:22]=[CH:23][CH:24]=3)[C:19]([NH:32][CH2:33][C:34]3[CH:39]=[CH:38][CH:37]=[CH:36][N:35]=3)=[N:18][N:17]=2)[CH:13]=[N:12][CH:11]=1Participants
3
Conditions
- Temperature
- 50 °C
Procedure
To N-((2,2-dimethyl-1,3-dioxolan-4-yl)methyl)-5-(5-phenyl-4-((pyridin-2ylmethyl)amino)phthalazin-1-yl)nicotinamide (0.0200 g, 0.0370 mmol) was added TFA (0.00282 mL, 0.0370 mmol) at room temperature and was heated at 50° C. for 4 h. TFA was removed under reduced pressure and reaction mixture was diluted with saturated NaHCO3 (50 mL). The reaction mixture was extracted with EtOAc (3×30 mL). The combined organic extracts were dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure. The resulting residue was purified by preparative HPLC (Condition 14 as described in general methods) to afford N-(2,3-dihydroxypropyl)-5-(5-phenyl-4-((pyridin-2-ylmethyl)amino)phthalazin-1-yl)nicotinamide (0.0120 g, 65%). LCMS (Condition 7): retention time 1.59 min, [M+1]=507.2. HPLC (Condition 25): retention time 5.23 min, Purity 97.90%. 1H NMR (400 MHz, DMSO-d6) δ 3.21-3.49 (m, 4 H), 3.63-3.72 (m, 1 H), 4.55-4.60 (m, 1 H), 4.66 (d, J=4.0 Hz, 2 H), 4.84 (br s, 1 H), 6.32 (dd, J=4.0 Hz, J=4.4 Hz, 1 H), 7.22 (dd, J=4.8 Hz, J=6.8 Hz, 1 H), 7.28 (d, J=8.0 Hz, 1 H), 7.50-7.58 (m, 5 H), 7.68-7.73 (m, 2 H), 7.80 (dd, J=1.6 Hz, J=8.4 Hz, 1 H), 7.93 (dd, J=7.2 Hz, J=8.4 Hz, 1 H), 8.23 (d, J=4.8 Hz, 1 H), 8.51 (t, J=2.0 Hz, 1 H), 8.75 (t, J=5.6 Hz, 1 H), 8.98 (d, J=2.0 Hz, 1 H), 9.16 (d, J=2.0 Hz, 1 H).