Water → 3-(6-Aminopyridin-3-yl)-6-fluoro-7-(methylamino)-2,3-dihydrobenzo[e][1,3]oxazin-4-one
Reaction equation
[F:1][C:2]1[C:3]([NH:13][CH3:14])=[CH:4][C:5]2[O:10][CH2:9][NH:8][C:7](=[O:11])[C:6]=2[CH:12]=1.I[C:16]1[CH:17]=[CH:18][C:19]([NH2:22])=[N:20][CH:21]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].O>O1CCOCC1.[Cu]I>[NH2:22][C:19]1[N:20]=[CH:21][C:16]([N:8]2[C:7](=[O:11])[C:6]3[CH:12]=[C:2]([F:1])[C:3]([NH:13][CH3:14])=[CH:4][C:5]=3[O:10][CH2:9]2)=[CH:17][CH:18]=1Participants
Reactant 4
Product 1
Reagents, catalysts & solvents 2
Conditions
- Temperature
- 100 °C
Procedure
To 6-fluoro-7-(methylamino)-2,3-dihydrobenzo[e][1,3]oxazin-4-one (0.05 g, 0.25 mmol) and 5-iodopyridin-2-amine (0.067 g, 0.304 mmol) in dioxane (1 ml) was added potassium phosphate (0.08 g, 0.377 mmol). The reaction mixture was degassed for 5 minutes and to this was added trans-diamino cyclohexane (0.004 g, 0.03 mmol) followed by copper (I) iodide (0.006 g, 0.03 mmol) and the mixture heated to 100° C. for 1 hour. Water was added and the product extracted with ethyl acetate (3×10 ml), dried over anhydrous sodium sulfate and concentrated. The product was further purified by reverse phase HPLC (C18) to yield pure 3-(6-aminopyridin-3-yl)-6-fluoro-7-(methylamino)-2,3-dihydrobenzo[e][1,3]oxazin-4-one (0.017 g, 23%). RP-HPLC: 1.5 min; ES-MS (M+H)+=289.1; 1H-NMR (MeOH-d4) δ (ppm): 2.82 (s, 3), 5.4 (s, 2), 6.2 (d, 1), 6.6 (d, 1), 7.3 (d, 1), 7.4 (dd, 1), 7.8 (s, 1).
Workup
- customThe reaction mixture was degassed for 5 minutes
- extractionthe product extracted with ethyl acetate (3×10 ml)
- dry with materialdried over anhydrous sodium sulfate
- concentrationconcentrated
- customThe product was further purified by reverse phase HPLC (C18)
Sources & evidence
- ORD record
- ord-789ed5cb2c244a578e27973159f8f70e
- Source dataset
- uspto-grants-2007_04
- Patent number
- US07205296B2
Reaction notes
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