6-chloro-1,2,3,9-tetrahydrocarbazol-4-one

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 of 6-chloro-4-oxo-1,2,3,4-tetrahydrocarbazole (109 mg, 0.5 mmol) in THF is treated with NaH (60 mg, 60% dispersion in mineral oil, 1.5 mmol), stirred for 30 min., treated with phenylsulfonyl chloride (132 mg, 0.5 mmol), shaken for 8 h and concentrated in vacuo. The resultant residue is dissolved in ethyl acetate, washed with water and reconcentrated in vacuo to afford the title product which is used as is in Example 134. shaken for 8 h concentrated in vacuo The resultant residue is dissolved in ethyl acetate washed with water

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of cyclohexane-1,3-dione mono-(4-chlorophenyl) hydrazone (45 mmol) obtained in Example 131 and trifluoroacetic acid (30 mL) is heated to 80° C. for 16 h, cooled to room temperature, poured over ice water and filtered. The filtercake is dried and recrystallized from ethanol/water to afford the title product, 4.2 g (42% yield), identified by HPLC and mass spectral analyses. cooled to room temperature filtered The filtercake is dried recrystallized from ethanol/water

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

Procedure: 6-Chloro-1,2,3,9-tetrahydro-4H-carbazol-4-one (0.4042 g, 0.0018 mol) is added to a slurry of pentane-washed NaH (0.091 g, 0.0023 mol) in DMF (2 mL) and after stirring for 20 min, p-fluorobenzyl bromide (0.28 mL, 0.0023 mol) is added. Additional DMF (1 mL) is added and the mixture is stirred for 4 h, at which time the mixture is partitioned between aq. sodium bicarbonate and ethyl acetate. The combined organic layers are washed with water, dried over sodium sulfate and concentrated to dryness. The resulting solids are chromatographed on silica gel (200 mL) using dichloromethane/heptane (60/40 and 80/20) to give 0.5519 g (92%) of the title compound; mp 207-207.75° C.; MS (ESI+) for C19H15ClFNO m/z 328.1 (M+H)+; IR (drift) 1628, 1511, 1467, 1448, 1360, 1226, 1218, 1145, 1096, 878, 849, 840, 804, 764, 649 cm−1; 1H NMR (CDCl3) δ2.23, 2.58, 2.86, 5.27, 6.99, 7.16, 8.27. Anal. Calcd for C19H15ClFNO: C, 69.62; H, 4.61; N, 4.27. Found (av): C, 69.08; H, 4.50; N, 4.26. the mixture is stirred for 4 h, at which time the mixture is partitioned between aq. sodium bicarbonate and ethyl acetate The combined organic layers are washed with water dried over sodium sulfate concentrated to dryness The resulting solids are chromatographed on silica gel (200 mL)

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

Procedure: 6-Chloro-1,2,3,9-tetrahydro-4H-carbazol-4-one (0.4010 g, 0.0018 mol) is added to a slurry of pentane-washed NaH (0.0902 g, 0.0023 mol) in DMF (2 mL) and after stirring for 27 min, benzyl bromide (0.26 mL, 0.0022 mol) is added. After stirring for 2.5 h at room temperature, the mixture is partitioned between aq. sodium bicarbonate and ethyl acetate. The combined organic layers are dried over sodium sulfate and concentrated to dryness. The resulting solids are chromatographed on silica gel (200 mL) using dichloromethane/heptane (60/40 and 100/0) to give 0.5158 g (91%) of the title compound. An aliquot (0.0625 g) is recrystallized from ethyl acetate/heptane to give 0.0415 g of product; mp 196.5-197° C.; MS (ESI+) for C19H16ClNO m/z 310.1 (M+H)+; 1H NMR (CDCl3) δ2.24, 2.58, 2.87, 5.31, 6.99, 7.16, 7.29, 8.28. Anal. Calcd for C19H16ClNO: C, 73.66; H, 5.20; N, 4.52. Found: C, 73.18; H, 5.19; N, 4.58. After stirring for 2.5 h at room temperature the mixture is partitioned between aq. sodium bicarbonate and ethyl acetate The combined organic layers are dried over sodium sulfate concentrated to dryness The resulting solids are chromatographed on silica gel (200 mL)

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

Procedure: 6-Chloro-1,2,3,9-tetrahydro-4H-carbazol-4-one (0.4010 g, 0.0018 mol) is added to a slurry of pentane-washed NaH (0.0902 g, 0.0023 mol) in DMF (2 mL) and after stirring for 27 min, benzyl bromide (0.26 mL, 0.0022 mol) is added. After stirring for 2.5 h at room temperature, the mixture is partitioned between aq. sodium bicarbonate and ethyl acetate. The combined organic layers are dried over sodium sulfate and concentrated to dryness. The resulting solids are chromatographed on silica gel (200 mL) using dichloromethane/heptane (60/40 and 100/0) to give 0.5158 g (91%) of the title compound. An aliquot (0.0625 g) is recrystallized from ethyl acetate/heptane to give 0.0415 g of product; mp 196.5-197° C.; MS (ESI+) for C19H16ClNO m/z 310.1 (M+H)+; 1H NMR (CDCl3) δ2.24, 2.58, 2.87, 5.31, 6.99, 7.16, 7.29, 8.28. Anal. Calcd for C19H16ClNO: C, 73.66; H, 5.20; N, 4.52. Found: C, 73.18; H, 5.19; N, 4.58. After stirring for 2.5 h at room temperature the mixture is partitioned between aq. sodium bicarbonate and ethyl acetate The combined organic layers are dried over sodium sulfate concentrated to dryness The resulting solids are chromatographed on silica gel (200 mL)

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A suspension of 6-chloro-4-oxo-1,2,3,4-tetrahydrocarbazole (21.9 mg, 0.1 mmol) in isopropanol and concentrated HCl (50 μL) is treated with aminoguanidine bicarbonate (20.4 μg, 0.15 mmol), heated at 80° C. for 4 h, cooled to room temperature and concentrated in vacuo. The resultant residue is purified by HPLC to give the title compound, 15.8 mg (49% yield), identified by mass spectral and HPLC analyses, (M+H) 276; retention time 3.72 min. cooled to room temperature concentrated in vacuo The resultant residue is purified by HPLC

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A suspension of p-chlorophenylhydrazine hydrochloride (8.06 g, 45 mmol) in water is added over a 10 min. period to a solution of 1,3-cyclohexanedione (5.05 g, 45 mmol) in water, stirred for 16 h and filtered. The filtercake is washed with water and air-dried. The thus-obtained cyclohexane-1,3-dione mono-(4-chlorophenyl)-hydrazone (45 mmol th.) is dissolved in trifluoroacetic acid (TFA) (30 mL), heated at 80° C. for 16 h, cooled to room temperature, poured into ice-water and filtered. The filtercake is air-dried and recrystallized from ethanol/water to afford the title product as a tan solid, 4.2 g (42% yield) identified by NMR and mass spectral analyses. filtered The filtercake is washed with water air-dried cooled to room temperature filtered The filtercake is air-dried recrystallized from ethanol/water

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A suspension of p-chlorophenylhydrazine hydrochloride (8.06 g, 45 mmol) in water is added over a 10 min. period to a solution of 1,3-cyclohexanedione (5.05 g, 45 mmol) in water, stirred for 16 h and filtered. The filtercake is washed with water and air-dried. The thus-obtained cyclohexane-1,3-dione mono-(4-chlorophenyl)-hydrazone (45 mmol th.) is dissolved in trifluoroacetic acid (TFA) (30 mL), heated at 80° C. for 16 h, cooled to room temperature, poured into ice-water and filtered. The filtercake is air-dried and recrystallized from ethanol/water to afford the title product as a tan solid, 4.2 g (42% yield) identified by NMR and mass spectral analyses. filtered The filtercake is washed with water air-dried cooled to room temperature filtered The filtercake is air-dried recrystallized from ethanol/water

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