1-amino-1-methylurea

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

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

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: 1-Methylhydrazinecarboxamide was acylated with isobutyryl chloride in triethylamine and dichloromethane to give 2-isobutyryl-1-methylhydrazinecarboxamide.

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 4-bromobenzaldehyde (4.3 g, 23 mmol) and 1-amino-1-methylurea (2.5 g, 28 mmol) in EtOH (40 mL) was added AcOH (2.5 mL) and water (4.5 mL). The resulting solution was stirred overnight at 80° C. and allowed to cool to rt. A precipitate formed by the addition of Et2O (50 mL). The solids were collected by filtration and compound 51a was obtained as a white solid. Mass Spectrum (LCMS, ESI pos.): Calcd. for C9H10BrN3O: 256.0 (M+H). Found 256.1. to cool to rt The solids were collected by filtration

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 4-bromobenzaldehyde (4.3 g, 23 mmol) and 1-amino-1-methylurea (2.5 g, 28 mmol) in EtOH (40 mL) was added AcOH (2.5 mL) and water (4.5 mL). The resulting solution was stirred overnight at 80° C. and allowed to cool to rt. A precipitate formed by the addition of Et2O (50 mL). The solids were collected by filtration and compound 51a was obtained as a white solid. Mass Spectrum (LCMS, ESI pos.): Calcd. for C9H10BrN3O: 256.0 (M+H). Found 256.1. to cool to rt The solids were collected by filtration

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

Procedure: The title compound was prepared as a white solid in analogy to the synthesis of example 52 from 1-(1-(quinolin-6-ylmethyl)-1H-[1,2,3]triazolo[4,5-b]pyrazin-6-yl)ethanone and 1-methylhydrazine-carboxamide. 1H-NMR (400 MHz, DMSO-d6) δ ppm 9.68 (s, 1H), 8.89 (m, 1H), 8.36 (d, 1H), 8.03 (s, 1H), 8.01 (d, 1H), 7.82 (dd, 1H), 7.53 (dd, 1H), 6.75 (s, 2H), 6.21 (s, 2H) 2.50 (s, 3H), 2.49 (s, 3H). LCMS (method B): [MH]+=376, tR=1.88 min.

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

Procedure: A solution of 1-[3-(1-quinolin-6-yl-cyclopropyl)-[1,2,4]triazolo[4,3-b]pyridazin-6-yl]-ethanone (30 mg, 0.091 mmol), acetic acid (0.1 mL) and 1-methylhydrazinecarboxamide (16.2 mg, 0.18 mmol) in methanol (5 mL) was stirred at room temperature overnight. The solvent was removed in vacuo and the residue was diluted with DCM, washed with sat. aqueous NaHCO3. The organic layer was dried over Na2SO4, filtered and concentrated in vacuo. The residue was purified by flash chromatography in silica gel eluting with a CH2Cl2/MeOH gradient to afford the title compound (14.9 mg, 41%) as yellow solid. 1H-NMR (400 MHz, DMSO-d6) δ ppm 8.84 (dd, 1H), 8.30 (d, 1H), 8.22 (d, 1H), 8.13 (d, 1H), 7.94-7.92 (m, 2H), 7.70 (dd, 1H), 7.49 (dd, 1H), 6.64 (s, 2H), 3.21 (s, 3H), 2.16 (s, 3H), 1.78-1.75 (m, 2H), 1.68-1.65 (m, 2H). LCMS (method A): [MH]+=401, tR=4.11 min. The solvent was removed in vacuo the residue was diluted with DCM washed with sat. aqueous NaHCO3 The organic layer was dried over Na2SO4 filtered concentrated in vacuo The residue was purified by flash chromatography in silica gel eluting with a CH2Cl2/MeOH gradient

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

Procedure: The title compound (27 mg, 55%) was synthesized from 1-(3-(quinolin-6-ylmethyl)-[1,2,4]triazolo[4,3-b]pyridazin-6-yl)ethanone (40 mg, 0.132 mmol) and 1-methylhydrazine-carboxamide (23.5 mg, 0.264 mmol) using the same procedure as described in the synthesis of 37. 1H-NMR (400 MHz, DMSO-d6) δ ppm 9.06 (d, 1H), 8.73 (d, 1H), 8.17 (m, 4H), 8.00 (d, 1H), 7.79 (m, 1H), 6.69 (s, 2H), 4.82 (s, 2H), 3.27 (s, 3H), 2.32 (s, 3H). LCMS (method A): [MH]+=375.0, tR=3.79 min.

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

Procedure: The title compound was prepared from 1-methylhydrazine carboxamide and 1-[3-(7-fluoro-quinolin-6-ylmethyl)-imidazo[1,2-b]pyridazin-6-yl]-ethanone in analogy to the synthesis of example 1 in 21% yield. 1H-NMR (400 MHz, DMSO-d6) δ ppm 8.86 (dd, 1H), 8.31 (d, 1H), 8.05 (s, 2H), 7.97 (d, 1H), 7.77 (d, 1H), 7.72 (s, 1H), 7.47 (q, 1H), 6.54 (s, 2H), 4.58 (s, 2H), 3.19 (s, 3H), 2.37 (s, 3H). LCMS (method A): [MH]+=392, tR=4.76 min.

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