Hydrochloric Acid → N-(5-(2-Amino-4-pyrimidinyl)-2-(4-morpholinyl)phenyl)-2-(2-fluorophenyl)-3-methyl-4-quinolinamine

반응식

[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[C:17]([CH3:18])=[C:16]([NH:19][C:20]2[CH:21]=[C:22]([C:32]3[CH:37]=[CH:36][N:35]=[C:34]([NH:38]C(=O)C)[N:33]=3)[CH:23]=[CH:24][C:25]=2[N:26]2[CH2:31][CH2:30][O:29][CH2:28][CH2:27]2)[C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[N:9]=1.Cl.C(#N)C.[OH-].[Na+]>>[NH2:38][C:34]1[N:33]=[C:32]([C:22]2[CH:23]=[CH:24][C:25]([N:26]3[CH2:31][CH2:30][O:29][CH2:28][CH2:27]3)=[C:20]([NH:19][C:16]3[C:15]4[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=4)[N:9]=[C:8]([C:3]4[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=4[F:1])[C:17]=3[CH3:18])[CH:21]=2)[CH:37]=[CH:36][N:35]=1

참가 물질

반응물 4

HCID 313Hydrochloric Acid

HCID 6342Acetonitrile

HCID 14798Sodium Hydroxide

HCID 67508373N-(4-(3-(2-(2-Fluorophenyl)-3-methylquinolin-4-ylamino)-4-morpholinophenyl)pyrimidin-2-yl)acetamide

생성물 1

HCID 50906136N-(5-(2-Amino-4-pyrimidinyl)-2-(4-morpholinyl)phenyl)-2-(2-fluorophenyl)-3-methyl-4-quinolinamine

실험 절차

A solution of N-(4-(3-(2-(2-fluorophenyl)-3-methylquinolin-4-ylamino)-4-morpholinophenyl)pyrimidin-2-yl)acetamide (20 mg, 36 μmol) and concentrated aq. hydrochloric acid (1.50 mL, 18.0 mmol) in acetonitrile (4.00 mL, 76.6 mmol) was heated to 90° C. After 18 h the pH was made alkaline by addition of sodium hydroxide. The reaction mixture was partitioned between 30 mL ea EtOAc and water. The organic layer was stirred over anhydrous magnesium sulfate, filtered and the filtrate concentrated under reduced pressure to afford a yellow solid. The product was purified by chromatography on silica gel eluting with 5-10% MeOH in DCM to afford a colorless solid. 1H NMR (400 MHz, chloroform-d) δ ppm 8.07-8.27 (2H, m), 7.84 (1H, d, J=8.2 Hz), 7.51-7.67 (3H, m), 7.37-7.49 (2H, m), 7.27 (1H, t, J=7.4 Hz), 7.01-7.23 (5H, m), 6.78 (1H, br. s.), 5.10 (2H, br. s.), 3.87 (4H, t, J=4.5 Hz), 3.11 (4H, br. s.), 2.06-2.21 (3H, m). Mass Spectrum (ESI) m/e=507.2 (M+1).