2(1H)-Quinoxalinone,3,4-dihydro-3,3-dimethyl-(9CI)

General procedure: General procedure for the synthesis of 3a–3t: Representative procedure for 3h: 50percent aqueous sodium hydroxide (0.42 mL, 5 equiv) was added dropwise to astirred mixture of o-phenylene diamine 1a (CAUTION: toxic) (200 mg, 1 equiv), 4-(trichloromethyl)tetrahydro-2H-pyran-4-ol (812 mg, 2 equiv) and N-benzyl-N, N-diethylethanaminium chloride (42 mg, 0.1 equiv) in CH2Cl2 (0.1 M) cooledto 0 °C over a period of 10–20 s under nitrogen. The resulting mixture wasstirred at 0 °C and left to warm to room temperature with stirring over 18 h.The reaction was monitored by analytical HPLC–MS. When complete, thereaction mixture was diluted with water (10 mL) until any solid had dissolvedand the layers were separated. The aqueous layer was extracted with CH2Cl2(3 20 mL). The combined organic layers were dried (MgSO4), ltered andevaporated to afford the crude product which was puried by ash silicachromatography, elution gradient 0–50percent EtOAc in heptane. The resulting solidwas ltered through a Buchner funnel, rinsed with MTBE (2 10 mL), andcollected to afford 10, 2, 3, 40, 5, 6-hexahydro-30H-spiro[pyran-4, 20-quinoxalin]-30-one (310 mg, 77percent) as a pale yellow powder.1, 2, 3, 4-Tetrahydro-3, 3-dimethylquinoxalin-2-one (IV) A mixture of 1, 2-phenylenediamine (II, 7.55 g), ethyl 2-bromoisobutyrate (III, 12.8 ml), diisopropylamine (15.5 ml) and DMF (30 ml) is heated at 110 for 5 hr, after which an additional ethyl bromoisobutyrate (III, 0.5 ml) and diiopropylethylamine (0.8 ml) is added. After heating for 2 more hours, the reaction is cooled and the DMF is removed in under reduced pressure. The residue is stored overnight in the freezer and then partitioned between ethyl acetate, water, and saline. The phases are separated and the organic phase is dried over magnesium sulfate, the organic phase is removed under reduced pressure. The residue is chromatographed eluding with ethyl acetate/dichloromethane (20/80). The product crystallizes out in the column. The product is recrystallized from dichloromethane/hexane to give the title compound, mp 173-174; NMR (CDCl3) 1.41, 3.72, 6.67, 6.76, 6.87 and 8.50 delta.To a solution of 1, 2-phenylenediamine (16.96 g) in N, N-dimethylformamide Data for 3, 4-dihydro-3, 3-dimethylquinoxalin-2(1H)-one: 1H NMR (400 MHz, CDCl3) delta 7.84 (bs, 1H), 6.89 (dd, J=7.3, 7.3, 1H), 6.76 (dd, J=7.2, 7.3, 1H), 6.70 (d, J=7.6, 1H), 6.67 (d, J=6.9, 1H), 3.69 (bs, 1H), 1.41 (s, 6H).A solution of 1.14 g of benzyl(triethyl)ammonium chloride in 50 mL of methylene chloride was added to a mixture of 10.8 g (0.1 mol) of o-phenylenediamine, 16.2 mL of chloro-form, and 18.4 mL of acetone. The mixture was cooled, and 40 g of 50% aqueous sodium hydroxide was slowly added with vigorous stirring at such a rate that the temperature did not exceed 10C. The mixture was kept for 5-7 h at 10C and diluted with water, and the precipitate was filtered off and washed with water and methylene chloride-hexane (1 : 3). If necessary, the precipitate was recrystallized from methylene chlo-ride-hexane (1 : 3). Yield of 3, 3-dimethyl-3, 4-dihydro-quinoxalin-2(1H)-one [30] 3.4 g (76%). 1 H NMR spec-trum (400 MHz, DMSO-d 6 ), delta, ppm: 1.24 s (6H, CH 3 ), 5.67 s (1H, NH), 6.54 t (1H, H arom , J = 7.0 Hz), 6.62 d (1H, H arom , J = 7.5 Hz), 6.64-6.77 m (2H, H arom ), 9.99 s (1H, CONH). The product, 1.76 g (0.01 mol), was dissolved in 5 mL of DMF, 0.4 g (0.01 mol) of sodium hydride and 0.9 mL (0.01 mol) of propargyl bromide were added with stirring, and the mixture was left overnight. The mixture was then diluted with water, and the precipitate was filtered off and washed with water, methylene chloride, and hexane. Yield of 22 1.3 g (61%), mp 130-131C. 1 H NMR spectrum (400 MHz, DMSO-d 6 ), delta, ppm: 1.26 s (6H, CH 3 ), 2.84 s (1H, 'CH), 4.63 s (2H, CH 2 ), 5.90 s (1H, NH), 6.61-6.71 m (2H, H arom ), 6.84 t (1H, H arom , J = 7.3 Hz), 7.01 d (1H, H arom , J = 7.6 Hz). Mass spectrum: m/z 215 [M + H] + . Found, %: C 72.93; H 6.55; N 13.01. C 13 H 14 N 2 O. Calculated, %: C 72.87; H 6.59; N 13.07.

Molecular Weight:176.21
XLogP3:1.5
Hydrogen Bond Donor Count:2
Hydrogen Bond Acceptor Count:2
Exact Mass:176.094963011
Monoisotopic Mass:176.094963011
Topological Polar Surface Area:41.1
Heavy Atom Count:13
Complexity:225
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes