1-bromo-2-isothiocyanatobenzene

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

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

Procedure: To a solution of 4-cyano-2-hydroxyl aniline (1.0 g, 7.5 mmol) in ethanol (20 mL) was added 2-bromophenylisothiocyanate (1.0 mL, 7.5 mmol). After 24 h, the reaction mixture was concentrated under reduced pressure to give 2.0 g (77%) of N-(4-cyano-2-hydroxyphenyl)-N′-(2-bromophenyl) thiourea as a yellow solid which required no further purification. 1H NMR (400 MHz, DMSO) δ 10.8 (s, 1H), 10.1 (s, 1H), 9.6 (s, 1H), 8.7 (d, 1H), 7.7 (d, 1H), 7.6 (d, 1H), 7.4 (t, 1H), 7.25 (d, 1H and d, 2H); MS(EI) m/e 229 (100), 348 (75 (M+)), 462 (30), 695 (10). the reaction mixture was concentrated under reduced pressure

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

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

Procedure: To a solution of 143 mg (0.69 mmol) of (4S,5S)-amine 1 in pentane (2.0 mL) was added dropwise 93 microliters (0.69 mmol) of 2-bromophenyl isothiocyanate. After ˜48 h, a white precipitate was collected, rinsed with pentane and dried under reduced pressure to yield 155 mg (53%) of the title compound. a white precipitate was collected rinsed with pentane dried under reduced pressure

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

Procedure: To a solution of 143 mg (0.69 mmol) of (4S,5S)-amine 1 in pentane (2.0 mL) was added dropwise 93 microliters (0.69 mmol) of 2-bromophenyl isothiocyanate. After ˜48 h, a white precipitate was collected, rinsed with pentane and dried under reduced pressure to yield 155 mg (53%) of the title compound. a white precipitate was collected rinsed with pentane dried under reduced pressure

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

Procedure: To a solution of 4-cyano-2-hydroxyl aniline (1.0 g, 7.5 mmol) in ethanol (20 mL) was added 2-bromophenylisothiocyanate (1.0 mL, 7.5 mmol). After 24 h, the reaction mixture was concentrated under reduced pressure to give 2.0 g (77%) of N-(4-cyano-2-hydroxyphenyl)-N′-(2-bromophenyl) thiourea as a yellow solid which required no further purification. 1H NMR (400 MHz, DMSO) δ 10.8 (s, 1H), 10.1 (s, 1H), 9.6 (s, 1H), 8.7 (d, 1H), 7.7 (d, 1H), 7.6 (d, 1H), 7.4 (t, 1H), 7.25 (d, 1H and d, 2H); MS(EI) m/e 229 (100), 348 (75 (M+)), 462 (30), 695 (10). the reaction mixture was concentrated under reduced pressure

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

Procedure: To a solution of 4-cyano-2-hydroxyl aniline (1.0 g, 7.5 mmol) in ethanol (20 mL) was added 2-bromophenylisothiocyanate (1.0 mL, 7.5 mmol). After 24 h, the reaction mixture was concentrated under reduced pressure to give 2.0 g (77%) of N-(4-cyano-2-hydroxyphenyl)-N′-(2-bromophenyl) thiourea as a yellow solid which required no further purification. 1H NMR (400 MHz, DMSO) δ 10.8 (s, 1H), 10.1 (s, 1H), 9.6 (s, 1H), 8.7 (d, 1H), 7.7 (d, 1H), 7.6 (d, 1H), 7.4 (t, 1H), 7.25 (d, 1H and d, 2H); MS(EI) m/e 229 (100), 348 (75 (M+)), 462 (30), 695 (10). the reaction mixture was concentrated under reduced pressure

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

Procedure: To a solution of 6′-methoxy-7′,8′-dimethyl-2′,4′-dihydro-1′H-spiro[cyclobutane-1,3′-quinoline] (810 mg) in 4 mL dichloromethane was added 1-bromo-2-isothiocyanatobenzene (525 μL) at room temperature. The mixture was allowed to reflux overnight. Water was used to quench the mixture and EtOAc was used for extraction. The combined organic phases were washed with brine, dried and evaporated. The residue was passed through a column ( dichloromethane:EtOAc=10:2) to give N-(2-bromophenyl)-6′-methoxy-7′,8′-dimethyl-2′,4′-dihydro-1′H-spiro[cyclobutane-1,3′-quinoline]-1′-carbothioamide (1.5 g) as a white solid. 1H-NMR (300 MHz, CDCl3) δ=8.54-8.22 (d, J=6.95 Hz, 1H); 7.61-7.39 (m, 2H); 7.38-7.22 (m, 1H); 7.15-6.87 (m, 1H); 6.69 (s, 1H); 5.72-5.38 (d, J=13.1 Hz, 1H); 3.86 (s, 3H); 3.39-3.25 (d, J=13.1 Hz, 1H); 2.85-2.67 (m, 2H); 2.46-2.28 (m, 1H); 2.14 (s, 3H); 2.12 (s, 3H); 2.07-1.79 (m, 3H); 1.79-1.62 (m, 2H) ppm. to reflux overnight to quench the mixture and EtOAc was used for extraction The combined organic phases were washed with brine dried evaporated

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

Procedure: A solution of N,N-dimethyl-3-amino-6-chloro-2-hydroxybenzene sulfonamide (480 mg, 3.58 mmol) and 2-bromophenylisothiocyanate (0.53 μL, 3.94 mmol) in 10 mL of ethanol was stirred at room temperature for overnight. Purification by column chromatography on silica gel, eluting with ethyl acetate/hexane (gradient elution) gave the desired product (368 mg, 22%). EI-MS (m/z) 463.67, 465.66, 467.65, 468.64 (M+). Purification by column chromatography on silica gel eluting with ethyl acetate/hexane (gradient elution)

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

Procedure: A solution of N,N-dimethyl-3-amino-6-chloro-2-hydroxybenzenesulfonamide (50 mg, 0.2 mmol) and 2-bromophenylisothiocyanate (43 mg, 0.2 mmol) in 0.5 mL of N,N-dimethylformamide was stirred at room temperature for 3 hours. Purification by column chromatography on silica gel, eluting with ethyl acetate/hexane (30/70, v/v) to give the desired product (66 mg, 74%). EI-MS (m/z) 465.5 (M+). Purification by column chromatography on silica gel eluting with ethyl acetate/hexane (30/70

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

Procedure: Methyl 3-hydroxy-4-aminophenylacetate (2.97 g, 16.4 mmol) was dissolved in methanol (30 ml). Under stirring at room temperature, 2-bromophenyl isothiocyanate (2.65 ml, 19.7 mmol) was added to the resulting solution. The reaction mixture was then stirred at room temperature for 1.5 hours. Mercuric oxide (yellow) (3.55 g, 16.4 mmol) was added to the reaction mixture, followed by heating and refluxing for 50 minutes. After cooling the reaction mixture to room temperature, the insoluble matter was filtered off through Celite under reduced pressure. The filtrate was distilled under reduced pressure to remove the solvent. The residue was then purified by chromatography on a silica gel column, whereby from hexane-ethyl acetate (4:1) eluate fractions, ethyl 2-(2-bromophenylamino)-6-benzoxazolylacetate (3.87 g, 66%) was obtained as a colorless solid. The reaction mixture was then stirred at room temperature for 1.5 hours by heating refluxing for 50 minutes After cooling the reaction mixture to room temperature the insoluble matter was filtered off through Celite under reduced pressure The filtrate was distilled under reduced pressure to remove the solvent The residue was then purified by chromatography on a silica gel column, whereby from hexane-ethyl acetate (4:1) eluate fractions

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

Procedure: To a solution of 143 mg (0.69 mmol) of (4S,5S)-amine 1 in pentane (2.0 mL) was added dropwise 93 microliters (0.69 mmol) of 2-bromophenyl isothiocyanate. After ˜48 h, a white precipitate was collected, rinsed with pentane and dried under reduced pressure to yield 155 mg (53%) of the title compound. a white precipitate was collected rinsed with pentane dried under reduced pressure