tert-butyl N-(2-piperidin-2-ylethyl)carbamate

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Prepared analogously to Example 37a from 6-chloro-4-[1-(5-chloro-1H-benzimidazol-2-yl)-ethylamino]-7-hydroxycarbonyl-quinazoline, pentafluorophenyl-tetramethyluronium-hexafluorophosphate (PFTU), diisopropylethylamine and 2-(2-tert.-butyloxycarbonylamino-ethyl)-piperidine in DMSO at ambient temperature and subsequent treatment with trifluoroacetic acid.

反応条件: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of N-t-butoxycarbonyl 2-(piperidin-2-yl) ethylamine (8.1 g) and DIEA (14.1 mL) in CH3CN (29 mL) was added 2-fluoropyridine (3.5 mL) and the resulting mixture was heated in a sealed-tube at 100° C. for three days. Solvent was removed and the crude product was purified via column chromatography (20% EtOAc/hexane) to afford 3.9 g of N-t-butoxycarbonyl 2-[1-(pyrid-2-yl)piperidin-4-yl]ethylamine. 1H NMR (CDCl3) δ=8.16 (dd, J=1.8, 5.0 Hz, 1H), 7.44–7.38 (m, 1H), 6.61 (d, J=8.7 Hz, 1H), 6.53 (dd, J=5.0, 7.2, 1H 4.58 (bs, 1H), 4.23 (d, J=12.6 Hz, 2H), 3.15 (q, J=6.6 Hz, 2H), 2.76 (dt, J=2.7, 12.6 Hz, 2H), 1.75 (d, J=12.6 Hz, 2H), 1.55–1.35 (m, 11H), 1.28–1.15 (m, 3H); Solvent was removed the crude product was purified via column chromatography (20% EtOAc/hexane)

反応条件: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of N-t-butoxycarbonyl 2-(piperidin-2-yl) ethylamine (8.1 g) and DIEA (14.1 mL) in CH3CN (29 mL) was added 2-fluoropyridine (3.5 mL) and the resulting mixture was heated in a sealed-tube at 100° C. for three days. Solvent was removed and the crude product was purified via column chromatography (20% EtOAc/hexane) to afford 3.9 g of N-t-butoxycarbonyl 2-[1-(pyrid-2-yl)piperidin-4-yl]ethylamine. 1H NMR (CDCl3) δ=8.16 (dd, J=1.8, 5.0 Hz, 1H), 7.44–7.38 (m, 1H), 6.61 (d, J=8.7 Hz, 1H), 6.53 (dd, J=5.0, 7.2, 1H 4.58 (bs, 1H), 4.23 (d, J=12.6 Hz, 2H), 3.15 (q, J=6.6 Hz, 2H), 2.76 (dt, J=2.7, 12.6 Hz, 2H), 1.75 (d, J=12.6 Hz, 2H), 1.55–1.35 (m, 11H), 1.28–1.15 (m, 3H); Solvent was removed the crude product was purified via column chromatography (20% EtOAc/hexane)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Prepared analogously to Example 37a from 6-chloro-4-[1-(5-chloro-1H-benzimidazol-2-yl)-ethylamino]-7-hydroxycarbonyl-quinazoline, pentafluorophenyl-tetramethyluronium-hexafluorophosphate (PFTU), diisopropylethylamine and 2-(2-tert.-butyloxycarbonylamino-ethyl)-piperidine in DMSO at ambient temperature and subsequent treatment with trifluoroacetic acid.

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Prepared analogously to Example 37a from 6-chloro-4-[1-(5-chloro-1H-benzimidazol-2-yl)-ethylamino]-7-hydroxycarbonyl-quinazoline, pentafluorophenyl-tetramethyluronium-hexafluorophosphate (PFTU), diisopropylethylamine and 2-(2-tert.-butyloxycarbonylamino-ethyl)-piperidine in DMSO at ambient temperature and subsequent treatment with trifluoroacetic acid.

反応条件: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of N-t-butoxycarbonyl 2-(piperidin-2-yl)ethylamine (8.1 g) and DIEA (14.1 mL) in CH3CN (29 mL) was added 2-fluoropyridine (3.5 mL) and the resulting mixture was heated in a sealed-tube at 100° C. for three days. Solvent was removed and the crude product was purified via column chromatography (20% EtOAc/hexane) to afford 3.9 g of N-t-butoxycarbonyl 2-[1-(pyrid-2-yl)piperidin-4-yl]ethylamine. 1H NMR (CDCl3) δ=8.16 (dd, J=1.8, 5.0 Hz, 1H), 7.44-7.38 (m, 1H), 6.61 (d, J=8.7 Hz, 1H), 6.53 (dd, J=5.0, 7.2, 1H), 4.58 (bs, 1H), 4.23 (d, J=12.6 Hz, 2H), 3.15 (q, J=6.6 Hz, 2H), 2.76 (dt, J=2.7, 12.6 Hz, 2H), 1.75 (d, J=12.6 Hz, 2H), 1.55-1.35 (m, 1H), 1.28-1.15 (m, 3H); Solvent was removed the crude product was purified via column chromatography (20% EtOAc/hexane)

反応条件: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of N-t-butoxycarbonyl 2-(piperidin-2-yl) ethylamine (8.1 g) and DIEA (14.1 mL) in CH3CN (29 mL) was added 2-fluoropyridine (3.5 mL) and the resulting mixture was heated in a sealed-tube at 100° C. for three days. Solvent was removed and the crude product was purified via column chromatography (20% EtOAc/hexane) to afford 3.9 g of N-t-butoxycarbonyl 2-[1-(pyrid-2-yl)piperidin-4-yl]ethylamine. 1H NMR (CDCl3) δ=8.16 (dd, J=1.8, 5.0 Hz, 1H), 7.44–7.38 (m, 1H), 6.61 (d, J=8.7 Hz, 1H), 6.53 (dd, J=5.0, 7.2, 1H), 4.58 (bs, 1H), 4.23 (d, J=12.6 Hz, 2H), 3.15 (q, J=6.6 Hz, 2H), 2.76 (dt, J=2.7, 12.6 Hz, 2H), 1.75 (d, J=12.6 Hz, 2H), 1.55–1.35 (m, 11H), 1.28–1.15 (m, 3H); Solvent was removed the crude product was purified via column chromatography (20% EtOAc/hexane)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: The product from step A was mixed with PtO2 (640 mg) in HOAc (30 mL) and hydrogenation was carried out at 58 psi on a Parr apparatus for overnight. Catalyst was removed and solvent was evaporated under reduced pressure to give N-t-butoxycarbonyl 2-(piperidin-2-yl) ethylamine as a black liquid. Catalyst was removed solvent was evaporated under reduced pressure

反応条件: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of N-t-butoxycarbonyl 2-(piperidin-2-yl)ethylamine (8.1 g) and DIEA (14.1 mL) in CH3CN (29 mL) is added 2-fluoropyridine (3.5 mL) and the resulting mixture is heated in a sealed-tube at 100° C. for three days. Solvent is removed and the crude product is purified via column chromatography (20% EtOAc/hexane) to afford 3.9 g of N-t-butoxycarbonyl 2-[1-(pyrid-2-yl)piperidin-4-yl]ethylamine. Solvent is removed the crude product is purified via column chromatography (20% EtOAc/hexane)

反応条件: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of N-t-butoxycarbonyl 2-(piperidin-2-yl) ethylamine (8.1 g) and DIEA (14.1 mL) in CH3CN (29 mL) was added 2-fluoropyridine (3.5 mL) and the resulting mixture was heated in a sealed-tube at 100° C. for three days. Solvent was removed and the crude product was purified via column chromatography (20% EtOAc/hexane) to afford 3.9 g of N-t-butoxycarbonyl 2-[1-(pyrid-2-yl)piperidin-4-yl]ethylamine. 1H NMR (CDCl3) δ=8.16 (dd, J=1.8, 5.0 Hz, 1H), 7.44–7.38 (m, 1H), 6.61 (d, J=8.7 Hz, 1H), 6.53 (dd, J=5.0, 7.2, 1H 4.58 (bs, 1H), 4.23 (d, J=12.6 Hz, 2H), 3.15 (q, J=6.6 Hz, 2H), 2.76 (dt, J=2.7, 12.6 Hz, 2H), 1.75 (d, J=12.6 Hz, 2H), 1.55–1.35 (m, 11H), 1.28–1.15 (m, 3H); Solvent was removed the crude product was purified via column chromatography (20% EtOAc/hexane)