Hexamethylenetetramine → 6-Cyclopropoxy-1-methyl-2-oxo-1,2,3,4-tetrahydro-quinoline-7-carbaldehyde
Reaction equation
[C:1]([OH:7])([C:3](F)(F)F)=O.C1N2CN3CN(C2)CN1C3.[CH:18]1([O:21][C:22]2[CH:23]=[C:24]3[C:29](=[CH:30]C=2)[N:28]([CH3:32])[C:27](=[O:33])[CH2:26][CH2:25]3)[CH2:20][CH2:19]1>>[CH:18]1([O:21][C:22]2[CH:23]=[C:24]3[C:29](=[CH:30][C:3]=2[CH:1]=[O:7])[N:28]([CH3:32])[C:27](=[O:33])[CH2:26][CH2:25]3)[CH2:20][CH2:19]1Participants
Conditions
- Temperature
- 65 °C
Procedure
TFA (1.38 ml) solution of hexamethylenetetramine (58 mg, 0.42 mmol) was heated to 70° C. for 1 hour under nitrogen. Another TFA (0.69 ml) solution of 6-Cyclopropoxy-1-methyl-3,4-dihydro-1H-quinolin-2-one (30 mg, 0.138 mmol) was then added to the above at room temperature and the reaction mixture was heated to 65° C. for an overnight. It was then cooled to room temperature, quenched with water and extracted with ethyl acetate (30 ml). The combined fractions were dried (MgSO4) and the solvent was evaporated under reduced pressure. The residue was chromatographed using 40% ethylacetate/hexane to yield the title compound as a solid (13 mg, 37% yield). 1H NMR (400 MHz, CDCl3) δ 0.84–0.87 (4H, m), 2.64–2.267 (2H, m), 2.94–2.98 (2H, m), 3.35 (3H, s), 3.80–3.85 (1H, m), 7.17 (1H, s), 7.39 (1H, s), 10.33 (1H, s). m/z (APCI+) 246 (M+1). HPLC (aqueous 200 Mm ammonium acetate buffer/acetonitrile gradient, 3.0 ml/min, Hewlett Packard ODS Hypersil 5 μM, 125×4 mm column), 4.454 min.
Workup
- temperatureIt was then cooled to room temperature
- customquenched with water
- extractionextracted with ethyl acetate (30 ml)
- dry with materialThe combined fractions were dried (MgSO4)
- customthe solvent was evaporated under reduced pressure
- customThe residue was chromatographed
Sources & evidence
- ORD record
- ord-5c94cb972d4f4c1f8e35a9e07c54d858
- Source dataset
- uspto-grants-2006_10
- Patent number
- US07119207B2
Reaction notes
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