1-piperazin-1-ylpropan-1-one

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: Prepared as described in general procedure (P) using 1,1-dicyclohexyl-3-(5-formyl-thiazol-2-yl)-urea (60 mg, 0.18 mmol), 1-piperazinyl-1-propanone (39 mg, 0.22 mmol), catalytic acetic acid and sodium triacetoxyborohydride (47 mg, 0.22 mmol) to afford 12 mg (15%) of the desired product after purification. Prepared

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

Procedure: Prepared as described in general procedure (P) using 1,1-dicyclohexyl-3-(5-formyl-thiazol-2-yl)-urea (60 mg, 0.18 mmol), 1-piperazinyl-1-propanone (39 mg, 0.22 mmol), catalytic acetic acid and sodium triacetoxyborohydride (47 mg, 0.22 mmol) to afford 12 mg (15%) of the desired product after purification. Prepared

Conditions: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a high-pressure tube was added 6-bromopicolinaldehyde (1, 2.00 g, 10.7 mmol), 1-(piperazin-1-yl)propan-1-one (18, 3.82 g, 26.9 mmol), potassium carbonate (6.69 g, 48.4 mmol) and anhydrous DMF (12 mL). The tube was sealed and the reaction mixture was heated at 120° C. for 17 h. The reaction suspension was poured into water (100 mL) and the mixture was brought to pH 7 using 2 N aq. HCl (20 mL). The solution was extracted with CH2Cl2 (3×100 mL), washed with brine (300 mL), dried over Na2SO4, filtered and concentrated to a brown oil. The product was purified by silica gel chromatography eluting with 0-5% CH3OH in CH2Cl2 to afford the title compound (0.815 g, 31%) as an orange solid: 1H NMR (500 MHz, CDCl3) δ 9.89 (s, 1H), 7.68 (t, J=8.0 Hz, 1H), 7.33 (d, J=8.0 Hz, 1H), 6.84 (d, J=8.0 Hz, 1H), 3.84-3.73 (m, 2H), 3.68-3.59 (m, 2H), 2.40 (q, J=7.5 Hz, 2H), 1.19 (t, J=7.5 Hz, 3H). The tube was sealed The solution was extracted with CH2Cl2 (3×100 mL) washed with brine (300 mL) dried over Na2SO4 filtered concentrated to a brown oil The product was purified by silica gel chromatography eluting with 0-5% CH3OH in CH2Cl2

Conditions: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a high-pressure tube was added 6-bromopicolinaldehyde (1, 2.00 g, 10.7 mmol), 1-(piperazin-1-yl)propan-1-one (18, 3.82 g, 26.9 mmol), potassium carbonate (6.69 g, 48.4 mmol) and anhydrous DMF (12 mL). The tube was sealed and the reaction mixture was heated at 120° C. for 17 h. The reaction suspension was poured into water (100 mL) and the mixture was brought to pH 7 using 2 N aq. HCl (20 mL). The solution was extracted with CH2Cl2 (3×100 mL), washed with brine (300 mL), dried over Na2SO4, filtered and concentrated to a brown oil. The product was purified by silica gel chromatography eluting with 0-5% CH3OH in CH2Cl2 to afford the title compound (0.815 g, 31%) as an orange solid: 1H NMR (500 MHz, CDCl3) δ 9.89 (s, 1H), 7.68 (t, J=8.0 Hz, 1H), 7.33 (d, J=8.0 Hz, 1H), 6.84 (d, J=8.0 Hz, 1H), 3.84-3.73 (m, 2H), 3.68-3.59 (m, 2H), 2.40 (q, J=7.5 Hz, 2H), 1.19 (t, J=7.5 Hz, 3H). The tube was sealed The solution was extracted with CH2Cl2 (3×100 mL) washed with brine (300 mL) dried over Na2SO4 filtered concentrated to a brown oil The product was purified by silica gel chromatography eluting with 0-5% CH3OH in CH2Cl2

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

Procedure: A Parr shaker bottle was charged with a suspension of benzyl 4-propionylpiperazine-1-carboxylate (16), 10% palladium on carbon, 50% wet (900 mg) and absolute ethanol (100 mL). The Parr bottle was filled with 20 psi of hydrogen and shook for 3 h at rt. The resulting suspension was filtered through Celite and concentrated to yield the title compound (4.31 g, 93%) as a clear, colorless oil: 1H NMR (500 MHz, CDCl3) δ 3.75-3.63 (m, 2H), 3.48-3.42 (m, 2H), 2.87-2.80 (m, 4H), 2.34 (q, J=7.5 Hz, 2H), 1.98 (br s, 1H), 1.15 (t, J=7.5 Hz, 3H). The resulting suspension was filtered through Celite concentrated

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

Procedure: Prepared as described in general procedure (P) using 1,1-dicyclohexyl-3-(5-formyl-thiazol-2-yl)-urea (60 mg, 0.18 mmol), 1-piperazinyl-1-propanone (39 mg, 0.22 mmol), catalytic acetic acid and sodium triacetoxyborohydride (47 mg, 0.22 mmol) to afford 12 mg (15%) of the desired product after purification. Prepared

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

Procedure: Prepared as described in general procedure (P) using 1,1-dicyclohexyl-3-(5-formyl-thiazol-2-yl)-urea (60 mg, 0.18 mmol), 1-piperazinyl-1-propanone (39 mg, 0.22 mmol), catalytic acetic acid and sodium triacetoxyborohydride (47 mg, 0.22 mmol) to afford 12 mg (15%) of the desired product after purification. Prepared

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

Procedure: Prepared as described in general procedure (P) using 1,1-dicyclohexyl-3-(5-formyl-thiazol-2-yl)-urea (60 mg, 0.18 mmol), 1-piperazinyl-1-propanone (39 mg, 0.22 mmol), catalytic acetic acid and sodium triacetoxyborohydride (47 mg, 0.22 mmol) to afford 12 mg (15%) of the desired product after purification. Prepared