4-(2-METHOXYPHENOXY)ANILINE

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

Conditions: temp:130.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 3-bromo-4-chloro-6,7-dimethoxyquinoline (302 mg) and 4-(2-methoxyphenoxy)-aniline (236 mg) in cyclohexanol (5 ml) was stirred and heated at 130° C. for 24 hours. The mixture was cooled to ambient temperature and then filtered. The crystals were washed first with methanol and then with diethyl ether and then dried to give 4-(2-methoxyphenoxy)-anilino-3-bromo-6,7-dimethoxyquinoline (Compound 2) (180 mg, 37%). The mixture was cooled to ambient temperature filtered The crystals were washed first with methanol with diethyl ether and then dried

Conditions: temp:110.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of hydrogen chloride in ether (1 molar, 0.34 ml) was added to a mixture of 4-chloro-6,7-dimethoxy-3-fluoro-quinoline (80 mg) and 4-(2-methoxyphenoxy)-aniline (142 mg) in cyclohexanol (3 ml). The mixture was stirred and heated at 110° C. for 18 hours. The mixture was cooled to ambient temperature and then filtered. The crystals were washed with a small volume of diethyl ether and then dried to give 4-(2-methoxyphenoxy)-anilino-3-fluoro-6,7-dimethoxyquinoline (120 mg, 79%). The mixture was cooled to ambient temperature filtered The crystals were washed with a small volume of diethyl ether dried

Conditions: temp:130.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 3-bromo-4-chloro-6,7-dimethoxyquinoline (302 mg) and 4-(2-methoxyphenoxy)-aniline (236 mg) in cyclohexanol (5 ml) was stirred and heated at 130° C. for 24 hours. The mixture was cooled to ambient temperature and then filtered. The crystals were washed first with methanol and then with diethyl ether and then dried to give 4-(2-methoxyphenoxy)-anilino-3-bromo-6,7-dimethoxyquinoline (Compound 2) (180 mg, 37%). The mixture was cooled to ambient temperature filtered The crystals were washed first with methanol with diethyl ether and then dried

Conditions: temp:130.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 3-bromo-4-chloro-6,7-dimethoxyquinoline (302 mg) and 4-(2-methoxyphenoxy)-aniline (236 mg) in cyclohexanol (5 ml) was stirred and heated at 130° C. for 24 hours. The mixture was cooled to ambient temperature and then filtered. The crystals were washed first with methanol and then with diethyl ether and then dried to give 4-(2-methoxyphenoxy)-anilino-3-bromo-6,7-dimethoxyquinoline (Compound 2) (180 mg, 37%). The mixture was cooled to ambient temperature filtered The crystals were washed first with methanol with diethyl ether and then dried

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

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

Procedure: Compound 430C (1.81 g, 85%) was prepared from 4-chloro-3-cyano-5-methyl-pyrrolo[1,2-b]pyridazine-6-carboxylic acid methyl ester (prepared using the procedure of Example 1D) (1.25 g, 5.0 mmol) and 430B (1.08 g, 5.0 mmol) by a route analogous to that used for the preparation of compound 388D. It is a white solid, and has a retention time of 6.74 min (∠Cl, 8 min run). MS found, (M+H)+=429.2 prepared a retention time of 6.74 min (∠Cl, 8 min run)

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

Procedure: A mixture of 430A (7.34 g, 29.9 mmol) and 10% Pd/C (1.47 g, 20 wt %, 50 wt % H2O) was stirred under H2 balloon in MeOH (60 ml) for 12 h. The catalyst was removed by filtration on celite. The filtrate was concentrated in vacuo to give 430B (6.40 g, 99%) as a white solid. It has a retention time of 3.77 min (standard ∠Cl method, 8 min run). MS found: (M+H)+=216.1 The catalyst was removed by filtration on celite The filtrate was concentrated in vacuo

Conditions: temp:110.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of hydrogen chloride in ether (1 molar, 0.34 ml) was added to a mixture of 4-chloro-6,7-dimethoxy-3-fluoro-quinoline (80 mg) and 4-(2-methoxyphenoxy)-aniline (142 mg) in cyclohexanol (3 ml). The mixture was stirred and heated at 110° C. for 18 hours. The mixture was cooled to ambient temperature and then filtered. The crystals were washed with a small volume of diethyl ether and then dried to give 4-(2-methoxyphenoxy)-anilino-3-fluoro-6,7-dimethoxyquinoline (120 mg, 79%). The mixture was cooled to ambient temperature filtered The crystals were washed with a small volume of diethyl ether dried

Conditions: temp:130.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 3-bromo-4-chloro-6,7-dimethoxyquinoline (302 mg) and 4-(2-methoxyphenoxy)-aniline (236 mg) in cyclohexanol (5 ml) was stirred and heated at 130° C. for 24 hours. The mixture was cooled to ambient temperature and then filtered. The crystals were washed first with methanol and then with diethyl ether and then dried to give 4-(2-methoxyphenoxy)-anilino-3-bromo-6,7-dimethoxyquinoline (Compound 2) (180 mg, 37%). The mixture was cooled to ambient temperature filtered The crystals were washed first with methanol with diethyl ether and then dried