cyclopropylthiourea

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

Procedure: Isothiocyanato-cyclopropane (4 g) was mixed with ammonia (37% in water, 8 mL) and methanol (32 mL) at 0° C. and then stirred for 16 hours at room temperature. The mixture was then cooled to 0° C., filtered, washed with a little water and dried. The Cyclopropyl-thiourea (2.06 mmol) and 4-(2-Bromo-acetyl)-benzoic acid (2.06 mmol) were mixed in THF (12 mL). After stirring at room temperature for 5 minutes the mixture was heated to 80° C. for 2 hours. The mixture was then cooled to room temperature and filtered. The solid was washed with a small amount of diethylether and dried. m/z=261.0 in MS ES+, which was characterized by hplc and MS and used in the next step without any further purification. The mixture was then cooled to 0° C. filtered washed with a little water dried After stirring at room temperature for 5 minutes the mixture was heated to 80° C. for 2 hours The mixture was then cooled to room temperature filtered The solid was washed with a small amount of diethylether dried used in the next step without any further purification

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 2-Bromo-1-(1H-pyrrolo[2,3-b]pyridin-3-yl)-ethanone (prepared according to Galvez C. et al, J. Het. Chem. 21, 1984, p421-423) (0.90 g, 3.76 mmol) and cyclopropyl-thiourea (prepared according to Marletta, M. et al, J. Med. Chem. 35, 1992, p1137-1144) (0.46 g, 3.96 mmol) was heated in ethanol (20 mL), at reflux for 4 hours. The reaction mixture was cooled to 0° C. with and ice-water bath, then the solids were filtered and dried to give cyclopropyl-[4-(1H-pyrrolo[2,3-b]pyridin-3-yl)-thiazol-2-yl]-amine as a tan solid (1.2 g, 92%). LC/MS MH+ =257.02, LC/MS RT: 1.62 min. 1H NMR (500 MHz, DMSO-d6, ppm) 12.22 (s,1H), 9.20 (bs,1H), 8.42 (d,1H, J=7.82 Hz), 8.36 (dd,1H, J=4.81, 1.22 Hz), 8.00 (s,1H), 7.25 (m,1H), 6.12 (s,1H), 2.77 (t, 1H,J=4.75), 0.86 (m,2H), 0.71 (m,2H). at reflux for 4 hours the solids were filtered dried

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

Procedure: N-cyclopropylthiourea (6.2 g) and malononitrile (6.6 g) were reacted in the same method as described in Preparation 12 to give the pale yellow above-indicated compound(3.7 g). as described in Preparation 12

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

Procedure: Isothiocyanato-cyclopropane (4 g) was mixed with ammonia (37% in water, 8 mL) and methanol (32 mL) at 0° C. and then stirred for 16 hours at room temperature. The mixture was then cooled to 0° C., filtered, washed with a little water and dried. The Cyclopropyl-thiourea (2.06 mmol) and 4-(2-Bromo-acetyl)-benzoic acid (2.06 mmol) were mixed in THF (12 mL). After stirring at room temperature for 5 minutes the mixture was heated to 80° C. for 2 hours. The mixture was then cooled to room temperature and filtered. The solid was washed with a small amount of diethylether and dried. m/z=261.0 in MS ES+, which was characterized by hplc and MS and used in the next step without any further purification. The mixture was then cooled to 0° C. filtered washed with a little water dried After stirring at room temperature for 5 minutes the mixture was heated to 80° C. for 2 hours The mixture was then cooled to room temperature filtered The solid was washed with a small amount of diethylether dried used in the next step without any further purification