[S:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[NH:10][C@H:11]1[CH2:14][C@H:13]([NH:15][C:16]2[C:17]([C:22]([CH3:26])([CH3:25])[C:23]#N)=[N:18][CH:19]=[CH:20][N:21]=2)[CH2:12]1.C(OCC)(=[O:29])C.[OH-].[Na+]>O.S(=O)(=O)(O)O>[S:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[NH:10][C@H:11]1[CH2:12][C@H:13]([N:15]2[C:16]3=[N:21][CH:20]=[CH:19][N:18]=[C:17]3[C:22]([CH3:26])([CH3:25])[C:23]2=[O:29])[CH2:14]12-(3-((Trans-3-(benzo[d]thiazol-2-ylamino)cyclobutyl)amino)pyrazin-2-yl)-2-methylpropanenitrile (0.067 g, 0.184 mmol) was dissolved in a mixture of water (3 mL) and concentrated sulfuric acid (2 mL) and heated at 100° C. After 35 minutes the heat was turned off and the reaction allowed to cool in the oil bath over 90 minutes. Water (100 mL), ice (about 100 mL), and ethyl acetate (200 mL) were added followed by 5 N sodium hydroxide (15 mL). The phases were mixed and separated and the organic dried with magnesium sulfate before evaporating to dryness under reduced pressure. Purification using silica chromatography (dichloromethane to ethyl acetate gradient) gave the desired 5-(trans-3-(benzo[d]thiazol-2-ylamino)cyclobutyl)-7,7-dimethyl-5H-pyrrolo[2,3-b]pyrazin-6(7H)-one (0.061 g, 0.167 mmol, 91% yield) as a white solid. M+1: 366.2. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.45 (s, 6 H) 2.42-2.58 (m, 2 H) 3.45 (s, 2 H) 4.53-4.68 (m, 1 H) 5.31 (quin, J=8.46 Hz, 1 H) 6.53 (br. s, 1 H) 7.04-7.15 (m, 1 H) 7.30 (t, J=7.24 Hz, 1 H) 7.59 (d, J=8.22 Hz, 1 H) 7.61 (d, J=8.02 Hz, 1 H) 8.09 (d, J=3.33 Hz, 1 H) 8.13 (d, J=3.30 Hz, 1 H).
Wird geladen…
