[3-(4-chlorophenyl)-2-oxopropyl] acetate

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: This compound was synthesized by the procedure described above for Compound 1, reacting 1,6,7,8-tetrahydro-1-aza-as-indacene-2,3-dione 10 (0.36 g, 1.92 mmol) with 3-(4-chlorophenyl)-2-oxopropyl acetate 2 (0.54 g, 2.40 mmol). The crude acid was purified as described above for Compound 4 to give pure product Compound 5 as a bright yellow powder (94 mg, 14% yield): 1H NMR (400 MHz, DMSO-D6) δ 2.15 (quint., 2H) 3.05 (t, J=7.3 Hz, 2H) 3.28 (t, J=7.5 Hz, 2H) 4.32 (s, 2H) 7.33 (s, 4H) 7.49 (d, J=8.3 Hz, 1H) 8.36 (d, J=8.1 Hz, 1H); HRMS (ESI+) calcd for C20H17ClNO3 (MH+) 354.0892, found 354.0898. This compound was synthesized by the procedure The crude acid was purified

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

Procedure: This compound was synthesized by the procedure described above for Compound 1, reacting 1,6,7,8-tetrahydro-1-aza-as-indacene-2,3-dione 10 (0.36 g, 1.92 mmol) with 3-(4-chlorophenyl)-2-oxopropyl acetate 2 (0.54 g, 2.40 mmol). The crude acid was purified as described above for Compound 4 to give pure product Compound 5 as a bright yellow powder (94 mg, 14% yield): 1H NMR (400 MHz, DMSO-D6) δ 2.15 (quint., 2H) 3.05 (t, J=7.3 Hz, 2H) 3.28 (t, J=7.5 Hz, 2H) 4.32 (s, 2H) 7.33 (s, 4H) 7.49 (d, J=8.3 Hz, 1H) 8.36 (d, J=8.1 Hz, 1H); HRMS (ESI+) calcd for C20H17ClNO3 (MH+) 354.0892, found 354.0898. This compound was synthesized by the procedure The crude acid was purified

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

Procedure: This compound was synthesized according to the procedure described above for Compound 2, reacting 5-trifluoromethoxyisatin (1.4 g, 6.06 mmol) with 3-(4-chlorophenyl)-2-oxopropyl acetate, Intermediate 2 (1.72 g, 7.57 mmol). The crude acid was recrystallized from ethanol to give pure product as a yellow powder Compound 14 (1.2 g, 50% yield): 1H NMR (400 MHz, DMSO-D6) δ ppm 4.32 (s, 2H) 7.26-7.40 (m, 4H) 7.47 (d, J=9.09 Hz, 1H) 8.00 (d, J=8.84 Hz, 1H) 8.86 (s, 1H). This compound was synthesized The crude acid was recrystallized from ethanol

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

Procedure: This compound was synthesized according to the procedure described above for Compound 2, reacting 7-fluoroisatin (1.00 g, 6.06 mmol) with 3-(4-chlorophenyl)-2-oxopropyl acetate, Intermediate 2 (1.72 g, 7.57 mmol). The crude acid was purified as described above for Compound 3, then recrystallized from ethanol/benzene to give pure product as an off-white powder Compound 13 (0.206 g, 10% yield): 1H NMR (400 MHz, DMSO-D6) δ 4.34 (s, 2H) 7.37 (m, 5H) 7.55 (m, 1H) 8.34 (d, J=8.6 Hz, 1H). This compound was synthesized The crude acid was purified recrystallized from ethanol/benzene

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

Procedure: This compound was synthesized according to the procedure described above for Compound 2, reacting 7-(fur-3-yl)isatin, Intermediate 10 (0.84 g, 3.9 mmol) with 3-(4-chlorophenyl)-2-oxopropyl acetate, Intermediate 2 (1.11 g, 4.91 mmol). The crude acid was purified as described above for Compound 3 to give pure product, a mustard-yellow powder Compound 12 (0.217 g, 15% yield): 1H NMR (400 MHz, DMSO-D6) δ 4.40 (s, 2H) 7.09 (d, J=1.8Hz, 1H) 7.39 (q, J=8.6 Hz, 4H) 7.56 (dd, J=8.46, 7.5 Hz, 1H) 7.67 (t, J=1.8 Hz, 1H) 7.84 (dd, J=7.3, 1.3 Hz, 1H) 8.07 (s, 1H) 8.30 (dd, J=8.6, 1.0 Hz, 1H). This compound was synthesized The crude acid was purified to give pure product

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

Procedure: This compound was synthesized by the procedure described above for Compound 2, reacting 7-sec-butylisatin (1.00 g, 4.92 mmol) with 3-(4-chlorophenyl)-2-oxopropyl acetate (1.39 g, 6.15 mmol). The crude acid was purified as described above for Compound 3 and, after hydrochloric acid treatment of an acetonitrile/water solution of the triethylammonium salt, extracted into ethyl acetate (3×), washed with brine, dried over anhydrous magnesium sulfate, filtered, evaporated and lyophilized. It was then purified (preparative HPLC, eluting with acetonitrile/water/triethylamine), and converted back to the free acid and extracted and evaporated once more as described above. A final lyophilization step gave product Compound 10 as a fluffy, bright yellow solid (72 mg, 3.9% yield): 1H NMR (400 MHz, DMSO-D6) δ 0.74 (t, J=7.3 Hz, 3H) 1.22 (d, J=6.8 Hz, 3H) 1.61 (m, 2H) 3.91 (m, 1H) 4.32 (dd, 2H) 7.34 (m, 4H) 7.39 (d, J=6.1 Hz, 1H) 7.51 (dd, J=8.6, 7.3 Hz, 1H) 8.25 (dd, J=8.3, 1.3 Hz, 1H); HRMS (ESI/FTMS) calcd for C21H21ClNO3 (MH+) 370.1205, found 370.1204. Anal. Calcd for C21H20ClNO3: C, 68.20; H, 5.45; N, 3.79. Found: C, 67.97; H, 5.47; N, 3.53. This compound was synthesized by the procedure The crude acid was purified after hydrochloric acid treatment of an acetonitrile/water solution of the triethylammonium salt, extracted into ethyl acetate (3×) washed with brine dried over anhydrous magnesium sulfate filtered evaporated It was then purified (preparative HPLC, eluting with acetonitrile/water/triethylamine) extracted evaporated once more

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

Procedure: This compound was synthesized by the procedure described above for Compound 2, reacting 7-sec-butylisatin (1.00 g, 4.92 mmol) with 3-(4-chlorophenyl)-2-oxopropyl acetate (1.39 g, 6.15 mmol). The crude acid was purified as described above for Compound 3 and, after hydrochloric acid treatment of an acetonitrile/water solution of the triethylammonium salt, extracted into ethyl acetate (3×), washed with brine, dried over anhydrous magnesium sulfate, filtered, evaporated and lyophilized. It was then purified (preparative HPLC, eluting with acetonitrile/water/triethylamine), and converted back to the free acid and extracted and evaporated once more as described above. A final lyophilization step gave product Compound 10 as a fluffy, bright yellow solid (72 mg, 3.9% yield): 1H NMR (400 MHz, DMSO-D6) δ 0.74 (t, J=7.3 Hz, 3H) 1.22 (d, J=6.8 Hz, 3H) 1.61 (m, 2H) 3.91 (m, 1H) 4.32 (dd, 2H) 7.34 (m, 4H) 7.39 (d, J=6.1 Hz, 1H) 7.51 (dd, J=8.6, 7.3 Hz, 1H) 8.25 (dd, J=8.3, 1.3 Hz, 1H); HRMS (ESI/FTMS) calcd for C21H21ClNO3 (MH+) 370.1205, found 370.1204. Anal. Calcd for C21H20ClNO3: C, 68.20; H, 5.45; N, 3.79. Found: C, 67.97; H, 5.47; N, 3.53. This compound was synthesized by the procedure The crude acid was purified after hydrochloric acid treatment of an acetonitrile/water solution of the triethylammonium salt, extracted into ethyl acetate (3×) washed with brine dried over anhydrous magnesium sulfate filtered evaporated It was then purified (preparative HPLC, eluting with acetonitrile/water/triethylamine) extracted evaporated once more

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

Procedure: This compound was synthesized by the procedure described above for Compound 2, reacting 7-Bromo-1H-indole-2,3-dione (1.00 g, 4.42 mmol) with intermediate 2 (1.25 g, 5.53 mmol). The crude acid was purified as described above for Compound 3, then recrystallized from acetonitrile to give product as large, bright yellow crystals (Compound 9, 0.398 g, 23% yield): 1H NMR (400 MHz, DMSO-D6) δ 4.35 (s, 2H) 7.35 (m, 4H) 7.46 (dd, J=8.6, 7.6 Hz, 1H) 7.92 (dd, J=7.5, 1.1 Hz, 1H) 8.50 (dd, J=8.6, 1.3 Hz, 1H); HRMS (ESI/FTMS) calcd for C17H12BrClNO3 (MH+) 391.9684, found 391.9689. Anal. Calcd for C17H11BrClNO3: C, 52.00; H, 2.82; N, 3.57. Found: C, 51.72; H, 2.77; N, 3.53. This compound was synthesized by the procedure The crude acid was purified recrystallized from acetonitrile