Hydrazine → 3-Hydrazinyl-4-methyl-6-phenylpyridazine
Reaction equation
Cl[C:2]1[N:3]=[N:4][C:5]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)=[CH:6][C:7]=1[CH3:8].[NH2:15][NH2:16]>>[CH3:8][C:7]1[CH:6]=[C:5]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[N:4]=[N:3][C:2]=1[NH:15][NH2:16]Participants
Conditions
- Temperature
- 100 °C
Procedure
3,6-Dichloro-4-methylpyridazine (1.00 g, 6.1 mmol) was mostly dissolved in dioxane (22.5 mL) then added phenylboronic acid (0.82 g, 6.7 mmol), PdCl2(dppf)-CH2Cl2Adduct (0.25 g, 0.31 mmol) and a solution of cesium carbonate (6.0 g, 18 mmol) in water (7.5 mL). The reaction mixture was heated at 80° C. for 6 hours. The reaction mixture was concentrated under vacuum and the remaining solid was triturated with water. The solid was collected on a glass frit, washing well with water. The sample was purified by flash chromatography eluting with 1:4 ethyl acetate/hexane to afford 3-chloro-4-methyl-6-phenylpyridazine as an off-white solid. MS (ESI pos. ion) m/z: 205.2 (MH+). Step 2. 3-Chloro-4-methyl-6-phenylpyridazine (0.510 g, 2.49 mmol) was dissolved in hydrazine (1.56 ml, 49.8 mmol) then the reaction mixture was heated at 100° C. for 1.5 hours. The precipitate that had formed in the mixture was collected and washed with iPrOH. The solid was dried under high vacuum to afford 1-(4-methyl-6-phenylpyridazin-3-yl)hydrazine as a pale yellow solid. MS (ESI pos. ion) m/z: 201.1 (MH+). The remaining synthesis of 7-methoxy-N-((8-methyl-6-phenyl-[1,2,4]triazolo[4,3-b]pyridazin-3-yl)methyl)-1,5-naphthyridin-4-amine was conducted as described in general Method B.
Workup
- customThe precipitate that had formed in the mixture
- customwas collected
- washwashed with iPrOH
- customThe solid was dried under high vacuum
Sources & evidence
- ORD record
- ord-1015053bd66c4cf992258a2fa8d0336f
- Source dataset
- uspto-grants-2012_06
- Patent number
- US08198448B2
Reaction notes
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