3-chloro-4-[(2-fluorophenyl)methoxy]aniline

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: 4-Chloro-5-methylthieno[2,3-d]pyrimidine (commercially available from Maybridge Chemical Co. Ltd.) (0.092 g, 0.50 mmol) and 3-chloro-4-(2-fluorobenzyloxy)aniline (prepared according to the published method: WO 96/09294) (0.164 g, 0.65 mmol) were reacted in 2-propanol (3.5 ml) for 4 hours, according to Procedure A. The product was obtained as cream plates (0.156 g, 72%) with m.p. 193-196° C.; (Found: C, 55.17; H, 3.77; N, 9.56. C20H15ClFN3OS.HCl requires: C, 55.05; H, 3.70; N, 9.63%); δH [2H6]-DMSO 8.39 (1H, s, 2-H), 8.37 (1H, br s, N—H), 7.75 (1H, d, J 4, 2′-H), 7.49-7.59 (2H, m), 7.34-7.44 (1H, m), 7.15-7.32 (4H, m) (6-H, 5′-H, 6′-H, 3″-H, 4″-H, 5″-H, 6″-H), 5.19 (2H, s, CH2), 2.69 (3H, s, 5-CH3); m/z 400 (M+1+). The product was obtained as cream plates (0.156 g, 72%) with m.p. 193-196° C.

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

Procedure: 4-Chlorothieno[3,2-d]pyrimidine (0.103 g, 0.60 mmol) and 3-chloro-4-(2-fluorobenzyloxy)aniline (prepared according to the published method: WO 96/09294) (0.197 g, 0.78 mmol) were reacted in 2-propanol (4.5 ml) for 4.5 hours, according to Procedure A. The product was obtained as cream prisms (0.208 g, 82%) with m.p. 231-233° C.; (Found: C, 53.39; H, 3.30; N, 9.79. C19H13ClFN3OS.HCl.H2O requires: C, 53.47; H, 3.42; N, 9.85%); δH [2H6]-DMSO 8.88 (1H, s, 2-H), 8.47 (1H, d, J 7, 6 H or 7 H) 7.88 (1H, d, J 5, 2′-H), 7.55-7.68 (3H, m), 7.33-7.49 (2H, m), 7.20-7.30 (2H, m) (6H or 7H, 5′-H, 6′-H, 3″-H, 4″-H, 5″-H, 6″-H), 5.29 (2H, s, CH2); m/z 385 (M+1+).

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

Procedure: 4-Chlorothieno[3,2-d]pyrimidine (0.103 g, 0.60 mmol) and 3-chloro-4-(2-fluorobenzyloxy)aniline (prepared according to the published method: WO 96/09294) (0.197 g, 0.78 mmol) were reacted in 2-propanol (4.5 ml) for 4.5 hours, according to Procedure A. The product was obtained as cream prisms (0.208 g, 82%) with m.p. 231-233° C.; (Found: C, 53.39; H, 3.30; N, 9.79. C19H13ClFN3OS.HCl.H2O requires: C, 53.47; H, 3.42; N, 9.85%); δH [2H6]-DMSO 8.88 (1H, s, 2-H), 8.47 (1H, d, J 7, 6 H or 7 H) 7.88 (1H, d, J 5, 2′-H), 7.55-7.68 (3H, m), 7.33-7.49 (2H, m), 7.20-7.30 (2H, m) (6H or 7H, 5′-H, 6′-H, 3″-H, 4″-H, 5″-H, 6″-H), 5.29 (2H, s, CH2); m/z 385 (M+1+).

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

Procedure: The title compound was prepared according to Procedure A from 3-chloro4-(2-fluoro-benzyloxy)aniline and 4-chloro-6-(5-methyl-1,3,4-oxadiazol-2-yl)-quinazoline; δH [2H6]DMSO 11.64(1H,bs), 9.40(1H,s), 8.97(1H,s), 8.58(1H,d), 8.11(1H,d), 7.94(1H,d), 7.71(1H,dd), 7.63(1H,dd), 7.45(2H,m), 7.30(2H,m), 5.31 (2H,s), 2.68(3H,s); m/z (M+1+) 462.

Conditions: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In a glass flask provided with a condenser, thermometer, mechanical stirrer and nitrogen inlet, —under nitrogen flow—15.0 g of 3-chloro-4-[(2-fluorobenzyl)oxy]aniline of formula (IV), 17.49 g of 4-chloro-6-iodoquinazoline of formula (VIII) (available in the market), 300 mL of Isopropanol were introduced. The reaction mixture was stirred at 70° C. for 2 hrs. Upon completing the reaction cooling was carried out at ambient temperature. The formed yellow solid was filtered washing the solid with 20 mL of cold Isopropanol. 31.9 g of product equivalent to a 98.7% molar yield were obtained. 1H-NMR spectrum according to FIG. 5. In a glass flask provided with a condenser cooling was carried out at ambient temperature The formed yellow solid was filtered washing the solid with 20 mL of cold Isopropanol

Conditions: temp:68.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In a glass flask provided with a condenser, thermometer, mechanical stirrer and nitrogen inlet, —under nitrogen flow—25.0 g of 2-Chloro-[(2-fluorobenzyl)oxy]-4-nitrobenzene of formula (V), 14.9 g of powder iron (MW: 55.85, 3.0 mol. equiv.), 42.7 g of ammonium chloride (MW: 53.49, 9.0 mol. equiv.), 350 mL of Ethanol denatured with Methanol and 85 mL of purified water were introduced. The reaction mixture was stirred at reflux temperature (68° C.) for 2 hours. In a glass flask provided with a condenser were introduced

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

Procedure: 4-Chloro-5-methylthieno[2,3-d]pyrimidine (commercially available from Maybridge Chemical Co. Ltd.) (0.092 g, 0.50 mmol) and 3-chloro-4-(2-fluorobenzyloxy)aniline (prepared according to the published method: WO 96/09294) (0.164 g, 0.65 mmol) were reacted in 2-propanol (3.5 ml) for 4 hours, according to Procedure A. The product was obtained as cream plates (0.156 g, 72%) with m.p. 193-196° C.; (Found: C, 55.17; H, 3.77; N, 9.56. C20H15ClFN3OS.HCl requires: C, 55.05; H, 3.70; N, 9.63%); δH [2H6]-DMSO 8.39 (1H, s, 2-H), 8.37 (1H, br s, N—H), 7.75 (1H, d, J 4, 2′-H), 7.49-7.59 (2H, m), 7.34-7.44 (1H, m), 7.15-7.32 (4H, m) (6-H, 5′-H, 6′-H, 3″-H, 4″-H, 5″-H, 6″-H), 5.19 (2H, s, CH2), 2.69 (3H, s, 5-CH3); m/z 400 (M+1+). The product was obtained as cream plates (0.156 g, 72%) with m.p. 193-196° C.

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

Procedure: 4-Chlorothieno[3,2-d]pyrimidine (0.103 g, 0.60 mmol) and 3-chloro-4-(2-fluorobenzyloxy)aniline (prepared according to the published method: WO 96/09294) (0.197 g, 0.78 mmol) were reacted in 2-propanol (4.5 ml) for 4.5 hours, according to Procedure A. The product was obtained as cream prisms (0.208 g, 82%) with m.p. 231-233° C.; (Found: C, 53.39; H, 3.30; N, 9.79. C19H13ClFN3OS.HCl.H2O requires: C, 53.47; H, 3.42; N, 9.85%); δH [2H6]-DMSO 8.88 (1H, s, 2-H), 8.47 (1H, d, J 7, 6 H or 7 H) 7.88 (1H, d, J 5, 2′-H), 7.55-7.68 (3H, m), 7.33-7.49 (2H, m), 7.20-7.30 (2H, m) (6H or 7H, 5′-H, 6′-H, 3″-H, 4″-H, 5″-H, 6″-H), 5.29 (2H, s, CH2); m/z 385 (M+1+).