1-iodo-4-isothiocyanatobenzene

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

Procedure: A mixture of 5,6-Dihydro-cyclopenta[b]thiophen-4-one (1.0 g, 7.4 mmol) and 1-Iodo-4-isothiocyanato-benzene (1.5 g, 7.2 mmol) in THF (2.0 mL) was added to lithium hexamethyl disilane (7.0 mL, 7.2 mmol) dropwise at room temperature. The reaction mixture was stirred for 8 hr. Hydrazine monohydrate (0.4 mL, 7.9 mmol) and glacial acetic acid (0.5 mL) were added to the reaction mixture, which was then heated at the reflux temperature for 24 hr. The resulting mixture was added to water (30 mL) and then extracted with ethyl acetate. The target product was purified by gravity column chromatography (50% EtOAc in hexane) to give (4,7-Dihydro-1-thia-4,5-diaza-cyclopenta[a]pentalen-6-yl)-(4-iodo-phenyl)-amine as brown solid in 32% yield. was then heated at the reflux temperature for 24 hr extracted with ethyl acetate The target product was purified by gravity column chromatography (50% EtOAc in hexane)

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

Procedure: A mixture of 5,6-Dihydro-cyclopenta[b]thiophen-4-one (1.0 g, 7.4 mmol) and 1-Iodo-4-isothiocyanato-benzene (1.5 g, 7.2 mmol) in THF (2.0 mL) was added to lithium hexamethyl disilane (7.0 mL, 7.2 mmol) dropwise at room temperature. The reaction mixture was stirred for 8 hr. Hydrazine monohydrate (0.4 mL, 7.9 mmol) and glacial acetic acid (0.5 mL) were added to the reaction mixture, which was then heated at the reflux temperature for 24 hr. The resulting mixture was added to water (30 mL) and then extracted with ethyl acetate. The target product was purified by gravity column chromatography (50% EtOAc in hexane) to give (4,7-Dihydro-1-thia-4,5-diaza-cyclopenta[a]pentalen-6-yl)-(4-iodo-phenyl)-amine as brown solid in 32% yield. was then heated at the reflux temperature for 24 hr extracted with ethyl acetate The target product was purified by gravity column chromatography (50% EtOAc in hexane)

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

Procedure: Pipemidic acid (25 mg, 0.0824 mmol), 4-iodophenyl isothiocyanate (21.5 mg, 0.0824 mmol) and triethylamine (23 μL, 0.165 mmol) were used. Purification on silica yielded compound 3 in Table 1, below (36 mg, 77%). 1H NMR (300 MHz, CDCl3) δ 9.32 (s, 1H), 8.66 (s, 1H), 7.66 (d, J=6.94 Hz, 1H), 7.37 (s, 1H), 7.27 (s, 1H), 7.00 (d, J=7.44 Hz, 1H), 4.33 (q, J=6.90 Hz, 2H), 4.21-3.99 (m, 8H), 1.49 (t, J=7.14 Hz, 3H) ppm. Purification on silica yielded compound 3 in Table 1

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

Procedure: Prepared from ethyl (2-chloropyridin-3-yl)acetate (D. H. Bremner et al., Synthesis, 1997, 949) (750 mg, 3.8 mmol) and 4-iodophenyl isothiocyanate (1.0 g, 3.8 mmol) by the method of Example 1. Title compound obtained as an off-white solid (800 mg, 50%). δH (DMSO-d6) 10.34 (1H, br s), 8.33-8.30 (2H, m), 7.79 (2H, dt, J 2.0, 6.7 Hz), 7.43-7.31 (3H, m), 4.40 (2H, q, J=7.1 Hz), 1.40 (3H, t, J=7.1 Hz). LCMS (ES+) RT 4.31 minutes, 425 (M+H)+.

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

Procedure: Prepared from ethyl (2-chloropyridin-3-yl)acetate (D. H. Bremner et al., Synthesis, 1997, 949) (750 mg, 3.8 mmol) and 4-iodophenyl isothiocyanate (1.0 g, 3.8 mmol) by the method of Example 1. Title compound obtained as an off-white solid (800 mg, 50%). δH (DMSO-d6) 10.34 (1H, br s), 8.33-8.30 (2H, m), 7.79 (2H, dt, J 2.0, 6.7 Hz), 7.43-7.31 (3H, m), 4.40 (2H, q, J 7.1 Hz), 1.40 (3H, t, J 7.1 Hz). LCMS (ES+) RT 4.31 minutes, 425 (M+H)+.

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

Procedure: Prepared from ethyl (2-chloropyridin-3-yl)acetate (D. H. Bremner et al., Synthesis, 1997, 949) (750 mg, 3.8 mmol) and 4-iodophenyl isothiocyanate (1.0 g, 3.8 mmol) by the method of Example 1. Title compound obtained as an off-white solid (800 mg, 50%). δH (DMSO-d6) 10.34 (1H, br s), 8.33-8.30 (2H, m), 7.79 (2H, dt, J 2.0, 6.7 Hz), 7.43-7.31 (3H, m), 4.40 (2H, q, J 7.1 Hz), 1.40 (3H, t, J 7.1 Hz). LCMS (ES+) RT 4.31 minutes, 425 (M+H)+.

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

Procedure: A mixture of 5,6-Dihydro-cyclopenta[b]thiophen-4-one (1.0 g, 7.4 mmol) and 1-Iodo-4-isothiocyanato-benzene (1.5 g, 7.2 mmol) in THF (2.0 mL) was added to lithium hexamethyl disilane (7.0 mL, 7.2 mmol) dropwise at room temperature. The reaction mixture was stirred for 8 hr. Hydrazine monohydrate (0.4 mL, 7.9 mmol) and glacial acetic acid (0.5 mL) were added to the reaction mixture, which was then heated at the reflux temperature for 24 hr. The resulting mixture was added to water (30 mL) and then extracted with ethyl acetate. The target product was purified by gravity column chromatography (50% EtOAc in hexane) to give (4,7-Dihydro-1-thia-4,5-diaza-cyclopenta[a]pentalen-6-yl)-(4-iodo-phenyl)-amine as brown solid in 32% yield. was then heated at the reflux temperature for 24 hr extracted with ethyl acetate The target product was purified by gravity column chromatography (50% EtOAc in hexane)

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

Procedure: Pipemidic acid (25 mg, 0.0824 mmol), 4-iodophenyl isothiocyanate (21.5 mg, 0.0824 mmol) and triethylamine (23 μL, 0.165 mmol) were used. Purification on silica yielded compound 3 in Table 1, below (36 mg, 77%). 1H NMR (300 MHz, CDCl3) δ 9.32 (s, 1H), 8.66 (s, 1H), 7.66 (d, J=6.94 Hz, 1H), 7.37 (s, 1H), 7.27 (s, 1H), 7.00 (d, J=7.44 Hz, 1H), 4.33 (q, J=6.90 Hz, 2H), 4.21-3.99 (m, 8H), 1.49 (t, J=7.14 Hz, 3H) ppm. Purification on silica yielded compound 3 in Table 1