1-bromo-3-isothiocyanatobenzene

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

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

Procedure: The procedure of Referential Example 16 was repeated, except that 3-bromophenyl isothiocyanate (25.0 g) serving as a starting material was used, to thereby yield N-(3-bromophenyl)thiourea (19.4 g) as colorless crystals. Subsequently, The procedure of Referential Example 17 was repeated, to thereby yield 2-amino-5-bromobenzothiazole (1.21 g). Thereafter, The procedure of Referential Example 18 was repeated, to thereby yield the title compound (227 mg).

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

Procedure: The procedure of Referential Example 16 was repeated, except that 3-bromophenyl isothiocyanate (25.0 g) serving as a starting material was used, to thereby yield N-(3-bromophenyl)thiourea (19.4 g) as colorless crystals. Subsequently, The procedure of Referential Example 17 was repeated, to thereby yield 2-amino-5-bromobenzothiazole (1.21 g). Thereafter, The procedure of Referential Example 18 was repeated, to thereby yield the title compound (227 mg).

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-Bromo-3-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 (3-Bromo-phenyl)-(4,7-dihydro-1-thia-4,5-diaza-cyclopenta[a]pentalen-6-yl)-amine as brown solid in 34% 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-Bromo-3-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 (3-Bromo-phenyl)-(4,7-dihydro-1-thia-4,5-diaza-cyclopenta[a]pentalen-6-yl)-amine as brown solid in 34% 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: Step 1) A mixture of commercially available 3-bromophenylisothiocyanate (10.06 g, 47.0 mmol) and 2-aminopropionaldehyde dimethylacetal (5.96 mL, 47.0 mmol) in EtOH (50 mL) was refluxed for 1 h. Evaporated to dryness to give 1-(3-bromo-phenyl)-3-(2,2-dimethoxy-1-methyl-ethyl)-thiourea as an off-white solid (15.69 g, 100%). Step 2) A mixture of the above prepared 1-(3-bromo-phenyl)-3-(2,2-dimethoxy-1-methyl-ethyl)-thiourea (15.69 g, 47 mmol) in H2O (85 mL) and 37% HCl (8.5 mL) was refluxed for 4.5 h. Removed from oil bath, added ice and ice water (total volume: 250 mL), the precipitate was filtered off, washed several times with ice water and dried in vacuum at 60° C. to give the 1-(3-bromo-phenyl)-4-methyl-1H-imidazole-2-thiol as a light orange solid (8.71 g, 69%). Step 3) To a suspension of the above prepared 1-(3-bromo-phenyl)-4-methyl-1H-imidazole-2-thiol (6.00 g, 22 mmol) in acetic acid (20 mL) and water (5 mL) was added dropwise 35% H2O2 (13.4 mL, 156 mmol) within 15 min keeping the internal temperature below 60° C. Stirred at 23° C. for 30 min, poured onto ice, destroyed excess H2O2 by addition of sat. Na2SO3-sol., adjusted pH with 32% NaOH-sol. until pH 9 is reached, extracted with EtOAc (3×100 mL), the combined organic layers were washed with brine and dried over Na2SO4. Removal of the solvent in vacuum left a red oil, which was purified by silica gel column chromatography with EtOAc to give the 1-(3-bromo-phenyl)-4-methyl-1H-imidazole as a brown oil (3.80 g, 72%). Step 4) A mixture of the above prepared 1-(3-bromo-phenyl)-4-methyl-1H-imidazole (0.313 g, 1.31 mmol), bis(pinacolato)diboron (0.364 g, 1.438 mmol), potassium acetate (0.389 g, 3.96 mmol) and PdCl2(PPh3)2 (0.023 g, 3 mol %) in DMF at 100° C. for 2 h; then addition of Pd(OAc)2 (0.007 g, 3 mol %) and dppf (0.018 g, 3 mol %) and stirred at 100° C. overnight. This solution obtained was used directly.] according to the general procedure VI. Obtained as an off-white solid (0.140 g, 32%). MS (ISP) 394.0 [(M+H)+]; mp 126-132° C. was refluxed for 1 h Evaporated to dryness

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

Procedure: The procedure of Example 25 was repeated, except that the reactants consisted of 0.9 g. of 2-decyltetrahydro-2H-1,3-thiazine and 0.7 g. of 3-bromophenyl isothiocyanate. The product was recrystallized from ethanol to give N-(3-bromophenyl)-2-decyltetrahydro-2H-1,3-thiazine3-carbothioamide, m.p. 73°-4°. The following elemental microanalysis was obtained: The product was recrystallized from ethanol

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

Procedure: The procedure of Referential Example 16 was repeated, except that 3-bromophenyl isothiocyanate (25.0 g) serving as a starting material was used, to thereby yield N-(3-bromophenyl)thiourea (19.4 g) as colorless crystals. Subsequently, The procedure of Referential Example 17 was repeated, to thereby yield 2-amino-5-bromobenzothiazole (1.21 g). Thereafter, The procedure of Referential Example 18 was repeated, to thereby yield the title compound (227 mg).

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-Bromo-3-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 (3-Bromo-phenyl)-(4,7-dihydro-1-thia-4,5-diaza-cyclopenta[a]pentalen-6-yl)-amine as brown solid in 34% 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)