[OH:1][CH:2]1[CH2:7][CH2:6][N:5]([CH3:8])[CH2:4][CH2:3]1.[CH2:9]([N:17]1[CH:21]=[C:20]([C:22]([F:25])([F:24])[F:23])[N:19]=[C:18]1[CH:26]=O)[CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1.[CH2:28]([N:36]1[C:40]([C:41]([F:44])([F:43])[F:42])=[CH:39][N:38]=[C:37]1[CH:45]=[O:46])[CH2:29][C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1.[OH-].[Na+]>CS(O)(=O)=O.O>[CH3:8][N:5]1[CH2:6][CH2:7][CH:2]([O:1][CH:26]2[C:12]3[CH:13]=[CH:14][CH:15]=[CH:16][C:11]=3[CH2:10][CH2:9][N:17]3[C:18]2=[N:19][C:20]([C:22]([F:25])([F:24])[F:23])=[CH:21]3)[CH2:3][CH2:4]1.[CH3:8][N:5]1[CH2:6][CH2:7][CH:2]([O:46][CH:45]2[C:31]3[CH:32]=[CH:33][CH:34]=[CH:35][C:30]=3[CH2:29][CH2:28][N:36]3[C:37]2=[N:38][CH:39]=[C:40]3[C:41]([F:44])([F:43])[F:42])[CH2:3][CH2:4]1To a solution of 4-hydroxy-N-methylpiperidine (173 mg, 1.5 mmoles) in methanesulfonic acid (2.5 mL) is added a solution of the mixture of 1-phenethyl-4-trifluoromethyl-imidazole-2-carbaldehyde and 1-phenethyl-5-trifluoromethyl-imidazole-2-carbaldehyde (example 1B). The reaction mixture is stirred overnight at room temperature. Water is added and the mixture is basified to pH 9-10 with 12N NaOH. The aqueous phase is extracted three times with dichloromethane. The organic phase is dried over magnesium sulphate, filtered and the solvent is removed under reduced pressure. The residue is purified by silica gel chromatography using (CH2Cl2:MeOH:NH4OH) as eluent with a gradient from (99:5:0.1) to (95:5:0.5) to give pure 4-(1-methylpiperidin-4-yloxy)-2-trifluoromethyl-9,10-dihydro-4H-3,10a-diaza-benzo[f]azulene (compound 1a) and pure 4-(1-methylpiperidin-4-yloxy)-1-trifluoromethyl-9,10-dihydro-4H-3,10a-diaza-benzo[f]azulene (compound 1b).
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