HCID 66989160、化合物 → HCID 16733572、化合物
反応式
O=C1C2C(=CC=CC=2)C(=O)[N:3]1[CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][N:18]([CH2:33][CH2:34][C:35]1[CH:40]=[CH:39][C:38]([NH:41][S:42]([CH3:45])(=[O:44])=[O:43])=[CH:37][CH:36]=1)[CH2:19][CH2:20][O:21][C:22]1[CH:27]=[CH:26][C:25]([NH:28][S:29]([CH3:32])(=[O:31])=[O:30])=[CH:24][CH:23]=1>CN>[NH2:3][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][N:18]([CH2:33][CH2:34][C:35]1[CH:40]=[CH:39][C:38]([NH:41][S:42]([CH3:45])(=[O:44])=[O:43])=[CH:37][CH:36]=1)[CH2:19][CH2:20][O:21][C:22]1[CH:23]=[CH:24][C:25]([NH:28][S:29]([CH3:32])(=[O:30])=[O:31])=[CH:26][CH:27]=1参加物
3
実験手順
Crude N-[4-({2-[[6-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)hexyl](2-{4-[(methylsulfonyl)amino]phenyl}ethyl)amino]ethyl}oxy)phenyl]methanesulfonamide (142 mg) was dissolved in methylamine (33% in ethanol, 10 ml, 0.216) and left at 22° C. for 48 h. Excess reagent was evaporated under reduced pressure and the oily residue azeotroped with two further portions of ethanol. The crude product was dissolved in acetonitrile/water/acetic acid (5/4/, <2 ml), half applied to a Phenomenex Jupiter C18 HPLC column and eluted using the following gradient (flow rate=10 ml/min, AU 20.0, 214 nm, AU 10, 256 nm, A=0.1% TFA/water, B=90% acetonitrile/10% water/0.1% TFA): t=0 min: B=5%; t=10 min: B=5%; t=100 min: B=35%; t=115 min: B=100%; t=130 min: B=100%. Fractions containing mainly the slower eluting component (>90%) were pooled and evaporated to give the title compound (14.9 mg). The remaining crude was applied to the C18 column but with a modified gradient: t=0 min: B=5%; t=10 min: B=5%; t=15 min: B=10%; t=95 min: B=30%; t=110 min: B=100%; t=125 min: B=100%. Fractions containing mainly the desired product were combined and evaporated as before to yield the title compound (21.3 mg˜80% purity). The material was used without further purification.