2-isothiocyanato-1,3-dimethylbenzene

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of 4-amino-4-methoxy-7-(1-methylpiperidin-4-ylmethoxy)quinazoline (150 mg) in DMF (4.5 ml) was added to sodium hydride (60% dispersion in mineral oil, 0.03 g) and the reaction mixture was stirred at ambient temperature for 20 minutes. 2,6-Dimethylphenyl isothiocyanate (0.162 g) was added and the mixture was stirred at ambient temperature for 20 hours. The action mixture was evaporated and the residual solid was purified by column chromatography on silica using increasingly polar mixtures of methylene chloride and a 2M solution of ammonia in methanol as eluent. There was thus obtained the title compound (0.112 g); NMR Spectrum: (CDCl3) 1.44-1.61 (m, 2H), 1.87-2.08 (m, 5H), 2.32 (s, 3H), 2.36 (s, 6H), 2.94 (d, 2H), 4.04 (m, 5H), 7.1 (s, 1H), 7.19 (m, 3H), 7.29 (s, 1H), 8.69 (s, 1H), 8.9 (s, 1H), 13.37 (s, 1H); Mass Spectrum: M+H+ 466. the mixture was stirred at ambient temperature for 20 hours The action mixture was evaporated the residual solid was purified by column chromatography on silica using increasingly polar mixtures of methylene chloride

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: was obtained in a similar manner to the method specified in Example 6a) by reacting a mixture prepared from 0.74 g of N-ethyl-N,N-diisopropylamine in 40 ml of THF, 0.8 g of 3,4-diaminothiophene dihydrobromide and 0.47 g of 2,6-dimethylphenyl isothiocyanate. was obtained in a similar manner to the method

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of N-allyl glycine (17.4 g), 2,6-dimethylphenyl-isothiocyanate (20 g), triethylamine (20.2 g), and methylene chloride (150 mL) was heated at reflux for 3 hours. The reaction mixture was evaporated to dryness. The residual gum was dissolved in diethyl ether, then treated with etheral hydrogen chloride. A white solid formed. The solid was filtered and discarded. The filtrate was concentrated to a residue. The residue was chromatographed on silica gel (CH2Cl2) to give title compound (5.2 g) as an orange solid, m.p. 43°-46° C. Anal. Calcd. for. C14H16N2OS: C, 64.59; H, 6.19; N, 10.76. Found: C, 64.52; H, 6.08; N, 10.66. Mass spectrum (EI, M.+) m/z 260. was heated at reflux for 3 hours The reaction mixture was evaporated to dryness The residual gum was dissolved in diethyl ether treated with etheral hydrogen chloride A white solid formed The solid was filtered The filtrate was concentrated to a residue The residue was chromatographed on silica gel (CH2Cl2)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of the crude N-isopropyl glycine (21.2 g), 2,6-dimethylphenyl-isothiocyanate (16.3 g), triethyl amine (21.0 g) and chloroform (300 mL) was heated at reflux for 4 hours. The solvent was evaporated. The residue was dissolved in ethyl acetate (400 mL) and water (300 mL). The organic phase was washed with 2N HCl (2×300 mL), then with water. The organic phase was dried over anhydrous magnesium sulfate and evaporated to dryness. Crystallization from ethanol afforded the title compound (12.9 g) as a white solid, m.p. 135°-137° C. Anal. Calcd. for. C14H18N2OS: C, 64.09; H, 6.92; N, 10.68. Found: C, 63.99; H, 6.72; N, 10.67. Mass spectrum (+FAB, [M+H]+) m/z 263. was heated at reflux for 4 hours The solvent was evaporated The residue was dissolved in ethyl acetate (400 mL) The organic phase was washed with 2N HCl (2×300 mL) The organic phase was dried over anhydrous magnesium sulfate evaporated to dryness Crystallization from ethanol

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of N-ethyl glycine (9.2 g), 2,6-dimethylphenyl-isothiocyanate (8.2 g), triethylamine (10.1 g), and methylene chloride (150 mL) was heated at reflux for 3.5 hours. The mixture was evaporated to dryness. Purification was achieved through crystallization from ethanol. The title compound (2.3 g) was obtained as a white solid (2.3 g). m.p. 128°-131° C. Anal. Calcd. for. C13H16N2OS: C, 62.87; H, 6.49; N, 11.28. Found: C, 62.83; H, 6.50; N, 11.25. Mass spectrum (EI, M.+) m/z 248. was heated at reflux for 3.5 hours The mixture was evaporated to dryness Purification was achieved through crystallization from ethanol

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Crude 3-[3-(trifluoromethyl)phenoxy]azetidine from catalytic debenzylation of 30.0 g (0.078 mole) of 1-benzhydryl-3-[3-(trifluoromethyl)phenoxy]azetidine was dissolved in 100 ml of methylene chloride and treated dropwise under a nitrogen atmosphere with a solution of 12.7 g (0.078 mole) of 2,6-dimethylphenylisothiocyanate in 25 ml of methylene chloride. The product began to precipitate during the addition and an additional 50 ml of methylene chloride was added to facilitate stirring. After stirring overnight at ambient temperature, the product was collected by filtration (13.5 g, m.p. 196°-199° C.). A 6.0 g sample was recrystallized from isopropanol to give 5.3 g of product, m.p. 197°-199° C. to precipitate during the addition an additional 50 ml of methylene chloride was added After stirring overnight at ambient temperature the product was collected by filtration (13.5 g, m.p. 196°-199° C.) A 6.0 g sample was recrystallized from isopropanol

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Crude 3-[3-(trifluoromethyl)phenoxy]azetidine from catalytic debenzylation of 30.0 g (0.078 mole) of 1-benzhydryl -3-[3-(trifluoromethyl)phenoxy]azetidine was dissolved in 100 ml of methylene chloride and treated dropwise under a nitrogen atmosphere with a solution of 12.7 g (0.078 mole) of 2,6-dimethylphenylisothiocyanate in 25 ml of methylene chloride. The product began to precipitate during the addition and an addition 50 ml of methylene chloride was added to facilitate stirring. After stirring overnight at ambient temperature, the product was collected by filtration (13.5 g, m.p. 196°-199° C.). A 6.0 g sample was recrystallized from isopropanol to give 5.3 g of product, m.p. 197°-199° C. to precipitate during the addition an addition 50 ml of methylene chloride was added After stirring overnight at ambient temperature the product was collected by filtration (13.5 g, m.p. 196°-199° C.) A 6.0 g sample was recrystallized from isopropanol