methyl 2-sulfanylbenzoate

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution consisting of methyl thiosalicylate 28 (0.67 g, 4.0 mmol) in DMF was treated with NaH (0.19 g, 4.8 mmol as a 60% dispersion in mineral oil) and stirred at rt for approximately 5-10 minutes and then Example 27 (1 g, 4.3 mmol) was added followed by additional NaH (0.4 g, 10 mmol, as a 60% dispersion in mineral oil) and the reaction was heated at 100° C. for 30 minutes. The crude reaction mixture was poured into water, filtered, and the solid product washed with additional water, MeOH and hexanes. The product thus obtained was triturated with MeOH to yield 29 (0.51 g): 1H NMR (DMSO-d6) δ 8.16 (d, 2H, J=2.3 Hz), 7.71-7.61 (m, 2H), 6.91 (d, 1H, J=2.3 Hz), 6.63 (d, 1H, J=2.3 Hz), 3.95 (s, 3H), 3.89 (s, 3H); MS 335 (M+Na)+. as a 60% dispersion in mineral oil) and the reaction was heated at 100° C. for 30 minutes The crude reaction mixture filtered the solid product washed with additional water, MeOH and hexanes The product thus obtained was triturated with MeOH

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of methyl thiosalicylate (25.0 g, Aldrich) in methanol (95 ml) at 0° C. was added 2-butyl-2-ethylaziridine (20.0 g, Synthetic Example 1(f)) and the mixture was stirred at room temperature for 18 hours. Solvent was evaporated and toluene (200 ml) and sodium methoxide (8.2 g) were added. The mixture was heated to reflux for 4.5 hours, removing water through a Dean-Stark trap. Solvent was evaporated and the residue was partitioned between 5% HCl (500 ml) and dichloromethane (400 ml). The organic layer was separated, dried and concentrated. Crystallization from hexanes/ethyl acetate provided the title compound as a white solid (38.0 g), mp 92°-93° C. 1H NMR consistent with the proposed structure. Solvent was evaporated toluene (200 ml) and sodium methoxide (8.2 g) were added The mixture was heated to reflux for 4.5 hours removing water through a Dean-Stark trap Solvent was evaporated the residue was partitioned between 5% HCl (500 ml) and dichloromethane (400 ml) The organic layer was separated dried concentrated Crystallization from hexanes/ethyl acetate

Conditions: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A 25 mL reaction vessel was charged with (3E)-3-(5,5-dimethyl-4-morpholin-4-ylfuran-2(5H)-ylidene)-6-iodo-1,3-dihydro-2H-indol-2-one (100 mg, 0.23 mmol), methyl thiosalicylate (77 mg, 0.46 mmol), PdCl2(dppf).CH2Cl2 (19 mg, 0.023 mmol), cesium carbonate (225 mg, 0.69 mmol) and 8 mL of anhydrous DMF. The mixture was purged with nitrogen and heated in 90° C. bath for 2.5 hours. The mixture was cooled to room temperature, diluted with 50 mL of water and extracted with EtOAc (3×50 mL). The organic layers were combined, washed with saturated NaHCO3 (50 mL), brine (2×50 mL), dried over Na2SO4, and concentrated to give a brown oil. Purification of the oily mixture by silica gel chromatography eluted with 1-10% MeOH/CHCl3 provided methyl 2-{[(3E)-3-(5,5-dimethyl-4-morpholin-4-ylfuran-2(5H)-ylidene)-2-oxo-2,3-dihydro-1 H-indol-6-yl]thio}benzoate as a brown solid. Yield: 60 mg, 55%. A 25 mL reaction vessel The mixture was purged with nitrogen The mixture was cooled to room temperature diluted with 50 mL of water extracted with EtOAc (3×50 mL) washed with saturated NaHCO3 (50 mL), brine (2×50 mL) dried over Na2SO4 concentrated to give a brown oil Purification of the oily mixture by silica gel chromatography eluted with 1-10% MeOH/CHCl3

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The title compound was prepared as described in General Method 6 from 1.9 mmol of 3-bromo-5,6-dihydro-4-hydroxy-6-phenyl-6-(2-phenylethyl)-2H-pyran-2-one (prepared in example BBB), 2.2 mmol of methyl thiosalicylate and 2.1 mmol of piperidine in 30 mL of dichloromethane. The crude product was chromatographed on silica gel, eluting first with chloroform and then with 5% methanol in chloroform, to give the title compound (m.p. 91°-92° C.). 1H NMR (DMSO-d6) δ 2.25 (m, 2 H), 2.38 (m, 1 H), 2.62 (m, 1 H), 3.44 (q, 2 H), 3.82 (s, 3 H), 6.06 (bd, 1 H), 6.90 (t, 1 H), 7.05-7.52 (m, 11 H), 7.81 (dd, 1 H). The title compound was prepared The crude product was chromatographed on silica gel eluting first with chloroform