3-(6-Chloro-[1,2,4]triazolo[3,4-a]phthalazin-3-yl)-5-methylisoxazole → 3-(5-Methylisoxazol-3-yl)-6-(6-[morpholin-4-yl]pyridin-2-ylmethoxy)[1,2,4]triazolo-[3,4-alpha]phthalazine
Reaction equation
[N:1]1([C:7]2[N:12]=[C:11]([CH2:13][OH:14])[CH:10]=[CH:9][CH:8]=2)[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.Cl[C:16]1[C:25]2[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=2)[C:19]2=[N:26][N:27]=[C:28]([C:29]3[CH:33]=[C:32]([CH3:34])[O:31][N:30]=3)[N:18]2[N:17]=1>>[CH3:34][C:32]1[O:31][N:30]=[C:29]([C:28]2[N:18]3[N:17]=[C:16]([O:14][CH2:13][C:11]4[CH:10]=[CH:9][CH:8]=[C:7]([N:1]5[CH2:2][CH2:3][O:4][CH2:5][CH2:6]5)[N:12]=4)[C:25]4[C:20]([C:19]3=[N:26][N:27]=2)=[CH:21][CH:22]=[CH:23][CH:24]=4)[CH:33]=1Participants
3
Procedure
The reaction was carried out according to Example 1 step 4 using (6-(morpholin-4-yl)pyridin-2-yl)methanol (96 mg, 0.49 mmol) and 6-chloro-3-(5-methylisoxazol-3-yl)-[1,2,4]triazolo[3,4-α]phthalazine (141 mg, 0.49 mmol). The crude residue was purified by column chromatography on silica using 2% MeOH/CH2Cl2 containing 1% NH3 to yield, after recrystallisation from CH2Cl2/iso-hexanes, the desired phthalazine (101 mg, 46%). 1H NMR (360 MHz, CDCl3) δ 8.70 (1H, d, J=8.1 Hz), 8.31 (1H, d, J=8.0 Hz), 8.00-7.91 (1H, m), 7.85-7.78 (1H, m), 7.58-7.50 (1H, m), 6.97 (1H, d, J=7.2 Hz), 6.80 (1H, s), 6.61 (1H, d, J=8.5 Hz), 5.60 (2H, s), 3.82 (4H, t, J=5.1 Hz), 3.54 (4H, t, J=5.1 Hz), 2.57 (3H, s). m/z (ES+) 444 (M+H+).
Workup
- customThe crude residue was purified by column chromatography on silica using 2% MeOH/CH2Cl2 containing 1% NH3
- customto yield
- customafter recrystallisation from CH2Cl2/iso-hexanes
Sources & evidence
- ORD record
- ord-637bb99af09c46d49c30a0b8890bb5de
- Source dataset
- uspto-grants-2005_05
- Patent number
- US06900209B2
Reaction notes
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