1-(isocyanatomethyl)-2-methylbenzene

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: Using an analogous procedure to that described in Example 3, 2-methylbenzyl isocyanate was reacted with 4-amino-6-methoxy-7-(N-methylpiperidin-4-ylmethoxy)quinazoline. The resultant solid was purified by column chromatography on silica using increasingly polar mixtures of methylene chloride, methanol and a 1% aqueous ammonium hydroxide solution as eluent. There was thus obtained the title compound; NMR Spectrum: (CDCl3) 1.39-1.56 (m, 2H), 1.84-2.04 (m, 5H), 2.29 (s, 3H), 2.39 (s, 3H), 2.9 (d, 2H), 3.92 (s, 3H), 4.03 (d, 2H), 4.66 (d, 2H), 7.21 (m, 4H), 7.34 (m, 2H), 8.6 (s, 1H), 8.74 (s, 1H), 10.44 (t, 1H); Mass Spectrum: M+H+ 450. The resultant solid was purified by column chromatography on silica using increasingly polar mixtures of methylene chloride, methanol

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

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

Procedure: Following the synthetic procedure of 6a as described in Example 1, compound 6j (56% yield) was synthesized from benzo[d]isothiazol-3-one and 2-methylbenzyl isocyanate as a white solid. mp 184-186° C.; IR(CHCl3) 3281, 1705, 1652, 1528 cm−1; 1H-NMR (DMSO-d6) δ2.32 (s, 3H), 4.52 (d, J=5.9 Hz, 2H), 7.15-7.19 (m, 3H), 7.27-7.30 (m, 1H), 7.48 (t, J=7.6 Hz, 1H), 7.78 (t, J=8.2 Hz, 1H), 7.93 (d, J=8.2 Hz, 1H), 8.01 (d, J=8.2 Hz, 1H), 9.18 (t, J=5.9 Hz, 1H); ESIMS m/e 299 (M++1).

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

Procedure: Analogously to Example 1, 75 mg (0.5 mmol) of 1-methyl-1,3-dihydroimidazo[4,5-b]pyridin-2-one were reacted with 74 mg (0.5 mmol) of 1-isocyanatomethyl-2-methylbenzene in dioxane at 80° C. Yield: 11 mg (7%), M+H+: 297.05.

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

Procedure: Analogously to Example 1, 75 mg (0.5 mmol) of 1-methyl-1,3-dihydroimidazo[4,5-b]pyridin-2-one were reacted with 74 mg (0.5 mmol) of 1-isocyanatomethyl-2-methylbenzene in dioxane at 80° C. Yield: 11 mg (7%), M+H+: 297.05.

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

Procedure: In analogy to example 11, 300 mg (2.24 mmol) of 1H-indazol-3-ol were reacted with 395.5 mg (2.69 mmol) of 1-isocyanatomethyl-2-methylbenzene. Yield: 177 mg (18%), M+H+: 429.26.

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

Procedure: 105 mg (0.78 mmol) of 1H-indazol-3-ol were reacted in 3 ml of THF with 138.3 mg (0.94 mmol) of 1-isocyanatomethyl-2-methylbenzene to give 3-oxo-1,3-dihydro-indazole-2-carboxylic acid 2-methylbenzylamide. 50 mg (178 μmol) of this compound were stirred in 3 ml of pyridine with 40 mg (355 μmol) of triethylamine and 43 mg (266 μmol) of 4-methylpiperidine-1-carbonyl chloride at room temperature for 7 h. Addition of a further 120 mg of 4-methylpiperidine-1-carbonyl chloride and 100 mg of triethylamine in 3 portions was followed by stirring again for 7 h, concentration and purification by preparative HPLC (PR18, acetonitrile/water 0.1% TFA). Yield: 48 mg (66%), M+H+: 407.15.

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

Procedure: Using an analogous procedure to that described in Example 3, 2-methylbenzyl isocyanate was reacted with 4-amino-6-methoxy-7-(N-methylpiperidin-4-ylmethoxy)quinazoline. The resultant solid was purified by column chromatography on silica using increasingly polar mixtures of methylene chloride, methanol and a 1% aqueous ammonium hydroxide solution as eluent. There was thus obtained the title compound; NMR Spectrum: (CDCl3) 1.39-1.56 (m, 2H), 1.84-2.04 (m, 5H), 2.29 (s, 3H), 2.39 (s, 3H), 2.9 (d, 2H), 3.92 (s, 3H), 4.03 (d, 2H), 4.66 (d, 2H), 7.21 (m, 4H), 7.34 (m, 2H), 8.6 (s, 1H), 8.74 (s, 1H), 10.44 (t, 1H); Mass Spectrum: M+H+ 450. The resultant solid was purified by column chromatography on silica using increasingly polar mixtures of methylene chloride, methanol

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

Procedure: In analogy to example 11, 300 mg (2.24 mmol) of 1H-indazol-3-ol were reacted with 395.5 mg (2.69 mmol) of 1-isocyanatomethyl-2-methylbenzene. Yield: 177 mg (18%), M+H+: 429.26.

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

Procedure: 105 mg (0.78 mmol) of 1H-indazol-3-ol were reacted in 3 ml of THF with 138.3 mg (0.94 mmol) of 1-isocyanatomethyl-2-methylbenzene to give 3-oxo-1,3-dihydroindazole-2-carboxylic acid 2-methylbenzylamide. 50 mg (178 μmol) of this compound were stirred in 3 ml of pyridine with 40 mg (355 μmol) of triethylamine and 43 mg (266 μmmol) of 4-methylpiperidine-1-carbonyl chloride at room temperature for 7 h. Addition of a further 120 mg of 4-methylpiperidine-1-carbonyl chloride and 100 mg of triethylamine in 3 portions was followed by stirring again for 7 h, concentration and purification by preparative HPLC (PR18, acetonitrile/water 0.1% TFA). Yield: 48 mg (66%), M+H+: 407.15.