(5-chloro-2-methoxyphenyl)thiourea

反応条件: temp:10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of 1-(2-methoxy-5-chlorophenyl)-2-thiourea (1 mmole) in chloroform (10 mL) was cooled to 10° C. and treated with bromine (2.2 mmole) in chloroform (10 mL). The reaction was stirred at 10° C. for 20 mm and at room temperature for 0.5 h. The resulting suspension was heated at reflux for 0.5 h. The precipitate was collected via filtration (washed with CH2Cl2) to give 2-amino-4-methoxy-7-chlorobenzothiazole which was subjected to Steps A, B, C and D of Example 34 to give 2-amino-4-phosphonomethoxy-6-bromo-7-chloro benzothiazole (35.1). mp >220° C. (dec.). Anal. Calcd. for C8H7N2O4PSCIBr: C:25.72; H: 1.89; N:7.50. Found: C:25.66; H:1.67; N:7.23. The resulting suspension was heated at reflux for 0.5 h The precipitate was collected via filtration (washed with CH2Cl2)

反応条件: temp:10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of 1-(2-methoxy-5-chlorophenyl)-2-thiourea (1 mmole) in chloroform (10 mL) was cooled to 10° C. and treated with bromine (2.2 mmole) in chloroform (10 mL). The reaction was stirred at 10° C. for 20 min and at room temperature for 0.5 h. The resulting suspension was heated at reflux for 0.5 h. The precipitate was collected via filtration (washed with CH2Cl2) to give 2-amino-4-methoxy-7-chlorobenzothiazole which was subjected to Steps A, B, C and D of Example 27 to give 2-amino-4-phosphonomethoxy-6-bromo-7-chloro benzothiazole (28.1). mp>220° C.(dec.). Anal. calcd. for C8H7N2O4PSClBr: C: 25.72; H: 1.89; N: 7.50. Found: C: 25.66; H: 1.67; N: 7.23. The resulting suspension was heated at reflux for 0.5 h The precipitate was collected via filtration (washed with CH2Cl2)

反応条件: temp:10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of 1-(2-methoxy-5-chlorophenyl)-2-thiourea (1 mmole) in chloroform (10 mL) was cooled to 10° C. and treated with bromine (2.2 mmole) in chloroform (10 mL). The reaction was stirred at 10° C. for 20 min and at room temperature for 0.5 h. The resulting suspension was heated at reflux for 0.5 h. The precipitate was collected via filtration (washed with CH2Cl2) to give 2-amino-4-methoxy-7-chlorobenzothiazole which was subjected to Steps A, B, C and D of Example 34 to give 2-amino-4-phosphonomethoxy-6-bromo-7-chloro benzothiazole (35.1). mp>220° C.(dec.). Anal. Calcd. for C8H7N2O4PSClBr: C, 25.72; H, 1.89; N, 7.50. Found: C, 25.66; H, 1.67; N, 7.23. The resulting suspension was heated at reflux for 0.5 h The precipitate was collected via filtration (washed with CH2Cl2)

反応条件: temp:10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of 1-(2-methoxy-5-chlorophenyl)-2-thiourea (1 mmole) in chloroform (10 mL) was cooled to 10° C. and treated with bromine (2.2 mmole) in chloroform (10 mL). The reaction was stirred at 10° C. for 20 min and at room temperature for 0.5 h. The resulting suspension was heated at reflux for 0.5 h. The precipitate was collected via filtration (washed with CH2Cl2) to give 2-amino-4-methoxy-7-chlorobenzothiazole which was subjected to Steps A, B, C and D of Example 34 to give 2-amino-4-phosphonomethoxy-6-bromo-7-chloro benzothiazole (35.1). mp>220° C.(dec.). Anal. Calcd. for C8H7N2O4PSClBr: C, 25.72; H, 1.89; N, 7.50. Found: C, 25.66; H, 1.67; N, 7.23. The resulting suspension was heated at reflux for 0.5 h The precipitate was collected via filtration (washed with CH2Cl2)

反応条件: temp:10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of 1-(2-methoxy-5-chlorophenyl)-2-thiourea (1 mmole) in chloroform (10 mL) was cooled to 10° C. and treated with bromine (2.2 mmole) in chloroform (10 mL). The reaction was stirred at 10° C. for 20 mm and at room temperature for 0.5 h. The resulting suspension was heated at reflux for 0.5 h. The precipitate was collected via filtration (washed with CH2Cl2) to give 2-amino-4-methoxy-7-chlorobenzothiazole which was subjected to Steps A, B, C and D of Example 34 to give 2-amino-4-phosphonomethoxy-6-bromo-7-chloro benzothiazole (35.1). mp >220° C. (dec.). Anal. Calcd. for C8H7N2O4PSCIBr: C:25.72; H: 1.89; N:7.50. Found: C:25.66; H:1.67; N:7.23. The resulting suspension was heated at reflux for 0.5 h The precipitate was collected via filtration (washed with CH2Cl2)

反応条件: temp:10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of 1-(2-methoxy-5-chlorophenyl)-2-thiourea (1 mmole) in chloroform (10 mL) was cooled to 10° C. and treated with bromine (2.2 mmole) in chloroform (10 mL). The reaction was stirred at 10° C. for 20 mm and at room temperature for 0.5 h. The resulting suspension was heated at reflux for 0.5 h. The precipitate was collected via filtration (washed with CH2Cl2) to give 2-amino-4-methoxy-7-chlorobenzothiazole which was subjected to Steps A, B, C and D of Example 34 to give 2-amino-4-phosphonomethoxy-6-bromo-7-chloro benzothiazole (35.1). mp >220° C. (dec.). Anal. Calcd. for C8H7N2O4PSCIBr: C:25.72; H: 1.89; N:7.50. Found: C:25.66; H:1.67; N:7.23. The resulting suspension was heated at reflux for 0.5 h The precipitate was collected via filtration (washed with CH2Cl2)

反応条件: temp:10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of 1-(2-methoxy-5-chlorophenyl)-2-thiourea (1 mmole) in chloroform (10 mL) was cooled to 10° C. and treated with bromine (2.2 mmole) in chloroform (10 mL). The reaction was stirred at 10° C. for 20 min and at room temperature for 0.5 h. The resulting suspension was heated at reflux for 0.5 h. The precipitate was collected via filtration (washed with CH2Cl2) to give 2-amino-4-methoxy-7-chlorobenzothiazole which was subjected to Steps A, B, C and D of Example 34 to give 2-amino-4-phosphonomethoxy-6-bromo-7-chloro benzothiazole (35.1). mp>220° C.(dec.). Anal. Calcd. for C8H7N2O4PSClBr: C:25.72; H:1.89; N:7.50. Found: C:25.66; H:1.67; N:7.23. The resulting suspension was heated at reflux for 0.5 h The precipitate was collected via filtration (washed with CH2Cl2)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Following the procedure described for 26z by condensing 5-chloro-2-methoxyphenylthiourea gave 30z (light brown solid; 26% for two steps). 1H NMR (600 MHz, DMSO-d6): δ 7.81 (d, J=2.4 Hz, 1H), 7.75 (dd, J=9 Hz, 2.4 Hz, 1H), 7.42 (d, J=9 Hz, 1H), 3.83 (s, 3H), 2.84-2.75 (m, 2H), 2.58-2.52 (m, 1H), 2.33-2.28 (m, 1H), 1.90-1.74 (m, 4H). 13C NMR (150 MHz, DMSO-d6): δ 194.4, 169.8, 154.5, 148.9, 134.1, 130.2, 125.7, 122.6, 121.7, 116.3, 57.6, 42.9, 30.5, 24.4, 21.5.

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A suspension of 21z (0.73 g, 2.3 mmol) and N-(5-chloro-2-methoxyphenyl)thiourea (0.73 g, 2.53 mmol) in EtOH (25 mL) was refuxed for 30 min. Upon cooling, the product was collected by filtration and washed with cold ethanol to yield 22z as a pale yellow solid (0.40 g, 84%). Mp decomposition at 216° C. 1H NMR (600 MHz, DMSO-d6): δ 11.86 (br s, 1H) 9.93 (br s, 1H), 8.64 (d, J=2.4 Hz, 1H), 7.83 (s, 1H), 7.18 (s, 1H), 7.02 (d, J=8.4 Hz, 1H), 6.98 (dd, J=8.4 Hz, 2.4 Hz, 1H), 3.86 (s, 3H), 1.25 (s, 9H). 13C NMR (150 MHz, DMSO-d6): δ 176.7, 162.1, 158.9, 146.6, 140.2, 136.4, 130.5, 124.7, 124.2, 121.3, 117.3, 112.1, 91.0, 56.1, 38.8, 26.6. HRMS m/z (ESI) calcd. for C18H19ClN4O2S2 (M+H)+ 423.0711. Found 423.0713. Upon cooling the product was collected by filtration washed with cold ethanol

反応条件: temp:10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of 1-(2-methoxy-5-chlorophenyl)-2-thiourea (1 mmole) in chloroform (10 mL) was cooled to 10° C. and treated with bromine (2.2 mmole) in chloroform (10 mL). The reaction was stirred at 10° C. for 20 min and at room temperature for 0.5 h. The resulting suspension was heated at reflux for 0.5 h. The precipitate was collected via filtration (washed with CH2Cl2) to give 2-amino-4-methoxy-7-chlorobenzothiazole which was subjected to Steps A, B, C and D of Example 27 to give 2-amino-4-phosphonomethoxy-6-bromo-7-chloro benzothiazole (28.1). mp>220° C.(dec.). Anal. calcd. for C8H7N2O4PSClBr: C: 25.72; H: 1.89; N: 7.50. Found: C: 25.66; H: 1.67; N: 7.23. The resulting suspension was heated at reflux for 0.5 h The precipitate was collected via filtration (washed with CH2Cl2)

反応条件: temp:10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of 1-(2-methoxy-5-chlorophenyl)-2-thiourea (1 mmole) in chloroform (10 mL) was cooled to 10° C. and treated with bromine (2.2 mmole) in chloroform (10 mL). The reaction was stirred at 10° C. for 20 min and at room temperature for 0.5 h. The resulting suspension was heated at reflux for 0.5 h. The precipitate was collected via filtration (washed with CH2Cl2) to give 2-amino-4-methoxy-7-chlorobenzothiazole which was subjected to Steps A, B, C and D of Example 34 to give 2-amino-4-phosphonomethoxy-6-bromo-7-chloro benzothiazole (35.1). mp>220° C.(dec.). Anal. Calcd. for C8H7N2O4PSClBr: C, 25.72; H, 1.89; N, 7.50. Found: C, 25.66; H, 1.67; N, 7.23. The resulting suspension was heated at reflux for 0.5 h The precipitate was collected via filtration (washed with CH2Cl2)

反応条件: temp:10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of 1-(2-methoxy-5-chlorophenyl)-2-thiourea (1 mmole) in chloroform (10 mL) was cooled to 10° C. and treated with bromine (2.2 mmole) in chloroform (10 mL). The reaction was stirred at 10° C. for 20 mm and at room temperature for 0.5 h. The resulting suspension was heated at reflux for 0.5 h. The precipitate was collected via filtration (washed with CH2Cl2) to give 2-amino-4-methoxy-7-chlorobenzothiazole which was subjected to Steps A, B, C and D of Example 34 to give 2-amino-4-phosphonomethoxy-6-bromo-7-chloro benzothiazole (35.1). mp >220° C. (dec.). Anal. Calcd. for C8H7N2O4PSCIBr: C:25.72; H: 1.89; N:7.50. Found: C:25.66; H:1.67; N:7.23. The resulting suspension was heated at reflux for 0.5 h The precipitate was collected via filtration (washed with CH2Cl2)