3,5-difluorobenzene-1,2-diamine

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

実験手順: is obtained analogously to the reaction described in example 1 b) from 4-methyl-3-thienyl isothiocyanate and 3,5-difluoro-1,2-diaminobenzene. Crystalline solid, 1st melting point: 178-182° C., another crystallization with 2nd m.p.: 299-301° C. is obtained analogously to the reaction Crystalline solid, 1st melting point: 178-182° C., another crystallization with 2nd m.p.: 299-301° C.

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

実験手順: is obtained analogously to the reaction described in example 1 b) from 4-methyl-3-thienyl isothiocyanate and 3,5-difluoro-1,2-diaminobenzene. Crystalline solid, 1st melting point: 178-182° C., another crystallization with 2nd m.p.: 299-301° C. is obtained analogously to the reaction Crystalline solid, 1st melting point: 178-182° C., another crystallization with 2nd m.p.: 299-301° C.

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

実験手順: is obtained analogously to the reaction described in example 1 b) from 4-methyl-3-thienyl isothiocyanate and 3,5-difluoro-1,2-diaminobenzene. Crystalline solid, 1st melting point: 178-182° C., another crystallization with 2nd m.p.: 299-301° C. is obtained analogously to the reaction Crystalline solid, 1st melting point: 178-182° C., another crystallization with 2nd m.p.: 299-301° C.

反応条件: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Aldehyde 1e (2.05 g, 4.28 mmol), 1,2-diamino-3,5-difluorobenzene (617 mg, 4.28 mmol) and sodium bisulfite (891 mg, 8.57 mmol) were dissolved in N,N-dimethylacetamide (43 mL) and heated in a 120° C. oilbath for 21 hours. After cooling to room temperature, the mixture was diluted with ethyl acetate (100 mL) and washed with half-saturated aqueous sodium chloride solution (75 mL, a 1:1 mixture of deionized water and saturated aqueous sodium chloride solution). The aqueous layer was back-extracted with ethyl acetate (2×100 mL). All the organic extracts were combined, dried over magnesium sulfate, and concentrated to a brown tar (3.39 g). This crude material was purified by silica gel chromatography (eluting with a gradient of 70% to 100% ethyl acetate in hexanes), to give benzoimidazole product 1f (2.11 g, 81%) as a tan foam: 1H NMR (CD3OD) δ 8.46 (s, 1H), 8.41 (s, 1H), 8.29 (s, 1H), 7.87 (d, J=8.6 Hz, 1H), 7.46 (dd, J=1.3, 8.6 Hz, 1H), 7.13 (m, 1H), 6.84 (m, 1H), 5.99 (dd, J=2.3, 9.9 Hz, 1H), 4.60 (s, 2H), 4.01 (m, 1H), 3.86 (m, 1H), 3.32 (m, 2H, obscured by solvent peak) 2.67 (m, 1H), 2.28 (s, 3H), 2.18 (m, 2H), 1.89 (m, 1H), 1.73 (m, 2H), 1.47 (s, 9H), 1.13 (t, J=7.1 Hz, 1H). Anal. (C33H36F2N6O3.0.4 H2O) C, H, N, F. After cooling to room temperature washed with half-saturated aqueous sodium chloride solution (75 mL a 1:1 mixture of deionized water and saturated aqueous sodium chloride solution) The aqueous layer was back-extracted with ethyl acetate (2×100 mL) dried over magnesium sulfate concentrated to a brown tar (3.39 g) This crude material was purified by silica gel chromatography ( eluting with a gradient of 70% to 100% ethyl acetate in hexanes),

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

実験手順: A mixture of 1,2-diamino-3,5-difluorobenzene (1 g, 6.94 mmol) and 1,1′-thiocarbonyldiimidazole (2.05 g, 11.52 mmol) in 10 ml of tetrahydrofuran is stirred at room temperature for 16 hours. The reaction mixture is then concentrated under reduced pressure and the residue is dissolved in 100 ml of ethyl acetate and washed with water (2×30 ml). The organic phase is then dried over MgSO4, filtered and concentrated under reduced pressure to yield 763 mg of 2-mercapto-4,6-difluorobenzimidazole. Yield=61%. Analytical LC/MS (method B): retention time=2.49 min. m/z=186.95 (positive ion mode). The reaction mixture is then concentrated under reduced pressure the residue is dissolved in 100 ml of ethyl acetate washed with water (2×30 ml) The organic phase is then dried over MgSO4 filtered concentrated under reduced pressure