6-bromo-3,4-dihydro-1H-quinoline-2-thione

Conditions: temp:140.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred solution of 6-bromo-3,4-dihydroquinoline-2(1H)-thione (74-4; 1.0 g, 0.004 mol) in n-butanol (20 mL) was added acetic hydrazide (1.19 g, 0.016 mol) at room temperature. Reaction mass was allowed to stir at 140° C. for 5 h. The reaction mixture was cooled to room temperature, diluted with water (50 mL) and extracted with ethyl acetate (3×25 mL). The combined organic layer was washed with saturated aqueous sodium chloride solution, dried over sodium sulphate and concentrated under vacuum to afford the crude compound. Crude compound was purified by silica gel column chromatography to obtain title compound. MS (M+2): 266.0. Reaction mass The reaction mixture was cooled to room temperature extracted with ethyl acetate (3×25 mL) The combined organic layer was washed with saturated aqueous sodium chloride solution dried over sodium sulphate concentrated under vacuum to afford the crude compound Crude compound was purified by silica gel column chromatography

Conditions: temp:140.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred solution of 6-bromo-3,4-dihydroquinoline-2(1H)-thione (74-4; 0.17 g, 0.0007 mol) in n-butanol (2 mL) was added formic hydrazide (0.105 g, 0.0017 mol) at room temperature. Reaction mass was allowed to stir at 140° C. for 1 h under microwave irradiation conditions. The reaction mixture was cooled to room temperature, diluted with water (10 mL) and extracted with ethyl acetate (2×10 mL). The combined organic layer was washed with saturated aqueous sodium chloride solution, dried over sodium sulphate and concentrated under vacuum to afford title compound. MS (M+3): 252.2. Reaction mass The reaction mixture was cooled to room temperature extracted with ethyl acetate (2×10 mL) The combined organic layer was washed with saturated aqueous sodium chloride solution dried over sodium sulphate concentrated under vacuum

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred solution of 6-bromo-3,4-dihydroquinolin-2(1H)-one (74-3; 15.0 g, 0.066 mol) in toluene (150 mL) was added Lawesson's reagent (13.4 g, 0.033 mol). Reaction mass was refluxed at 100° C. for 3 h. The reaction mixture was concentrated and directly purified by silica gel column chromatography to obtain title compound. MS (M+2): 243.9. Reaction mass The reaction mixture was concentrated directly purified by silica gel column chromatography

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

Procedure: A flask containing the title compound from Example 22 Step A (100 mg, 0.413 mmol), acetic hydrazide (40.8 mg, 0.496 mmol) and cyclohexanol (2.00 ml, 0.413 mmol) was heated at reflux for 2 days. The reaction was then poured into water and extracted with ethyl acetate. The organic extracts were combined, washed with brine, dried over sodium sulfate, filtered and concentrated under reduced pressure. Purification by flash chromatography on silica gel (0-15% methanol in ethyl acetate) provided the title compound: LCMS m/z 265.99 [M+2+H]+; 1H NMR (500 MHz, CDCl3) δ 7.53 (br s, 1H), 7.50 (d, J=8.57 Hz, 1H), 7.35 (d, J=8.57 Hz, 1H), 3.13-3.11 (m, 2H), 3.00-2.98 (m, 2H), 2.74 (s, 3H). was heated at reflux for 2 days extracted with ethyl acetate washed with brine dried over sodium sulfate filtered concentrated under reduced pressure Purification by flash chromatography on silica gel (0-15% methanol in ethyl acetate)

Conditions: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A flask containing the title compound from Example 22, Step A (0.200 g, 0.826 mmol), formic hydrazide (0.099 g, 1.65 mmol) and cyclohexanol (6.00 ml, 0.826 mmol) was heated to 120° C. for 16 hours. The reaction was then cooled to room temperature, poured into water and extracted with ethyl acetate. The organic extracts were combined, washed with brine, dried over sodium sulfate, filtered and concentrated. Purification by flash chromatography on silica gel (0-15% methanol in ethyl acetate) provided the title compound: LCMS m/z 251.90 [M+2+H]+; 1H NMR (500 MHz, CD3OD) δ 9.12 (s, 1H), 7.63-7.54 (m, 3H), 3.19-3.16 (m, 2H), 3.11-3.08 (m, 2H). The reaction was then cooled to room temperature extracted with ethyl acetate washed with brine dried over sodium sulfate filtered concentrated Purification by flash chromatography on silica gel (0-15% methanol in ethyl acetate)

Conditions: temp:110.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 6-bromo-3,4-dihydroquinolin-2-(1H)-one (1.00 g, 4.42 mmol) and 2,4-bis(4-methoxyphenyl)-1,3,2,4-dithiadiphosphetane2,4-disulfide (0.895 g, 2.21 mmol) were suspended in toluene (110 mL) and then heated to 110° C. overnight. The reaction was then cooled to room temperature and concentrated under reduced pressure. Dichloromethane was added, giving a mixture that was filtered to provide the title compound: LCMS m/z 243.95 [M+2+H]+; 1H NMR (500 MHz, DMSO) δ 7.44 (s, 1H), 7.39 (d, J=8.4 Hz, 1H), 7.01 (d, J=8.4 Hz, 1H), 2.92-2.89 (m, 2H), 2.81-2.78 (m, 2H). The reaction was then cooled to room temperature concentrated under reduced pressure Dichloromethane was added giving a mixture that was filtered