1,4-diazepan-2-one

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

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

Procedure: A solution of 3-bromo-6-fluoropyridine (315 mg, 1.79 mmol), 1,4-diazepan-2-one (200 mg, 1.75 mmol), and triethylamine (0.269 ml, 1.93 mmol) in N,N-dimethylacetamide (3 mL) was irradiated in a microwave reactor for twenty minutes at 220° C. The reaction mixture was diluted with ethyl acetate (35 mL) and then washed with saturated aqueous sodium bicarbonate (15 mL), water (3×10 mL), and brine (15 mL). The organic layer was dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by chromatography on silica gel (0.5-8.5% methanol/dichloromethane) to afford 4-(5-bromopyridin-2-yl)-1,4-diazepan-2-one. MS ESI calc'd. for C10H13BrN3O [M+H]+ 270 and 272. found 270 and 272. 1H NMR (500 MHz, DMSO-d6): δ 8.14 (d, J=2.4 Hz, 1H), 7.68 (dd, J=9.1, 2.7 Hz, 1H), 7.48 (m, 1H), 6.70 (d, J=9.1 Hz, 1H), 4.11 (s, 2H), 3.85 (s, 2H), 3.18 (m, 2H), 1.62 (m, 2H). washed with saturated aqueous sodium bicarbonate (15 mL), water (3×10 mL), and brine (15 mL) The organic layer was dried over sodium sulfate filtered concentrated under reduced pressure The residue was purified by chromatography on silica gel (0.5-8.5% methanol/dichloromethane)

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

Procedure: Reaction of 5-chloro-1-methyl-4-nitro-1H-pyrazole and 1,4-diazepan-2-one gave 4-(1-methyl-4-nitro-1H-pyrazol-5-yl)-1,4-diazepan-2-one as an off-white solid (0.27 g, 92%). 1H NMR (400 MHz, CDCl3) δ 8.02 (s, 1H), 6.10 (s, 1H), 3.95-3.86 (m, 2H), 3.80 (s, 3H), 3.51-3.44 (m, 2H), 3.43-3.37 (m, 2H), 2.04-1.97 (m, 2H)

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

Procedure: Prepared analogously to Example 1d from (1S)-2-chloro-4-{N-[1-(5-chloro-1H-benzimidazol-2-yl)ethyl]aminocarbonyl}benzoic acid, PFTU, diisopropylethylamine, and [1,4]diazepan-2-one in dimethylformamide. Yield: 63%; C22H21Cl2N5O3 (474.346); mass spectrum: (M+H)+=474/476 (chlorine isotope).

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

Procedure: Reaction of 5-chloro-1-methyl-4-nitro-1H-pyrazole and 1,4-diazepan-2-one gave 4-(1-methyl-4-nitro-1H-pyrazol-5-yl)-1,4-diazepan-2-one as an off-white solid (0.27 g, 92%). 1H NMR (400 MHz, CDCl3) δ 8.02 (s, 1H), 6.10 (s, 1H), 3.95-3.86 (m, 2H), 3.80 (s, 3H), 3.51-3.44 (m, 2H), 3.43-3.37 (m, 2H), 2.04-1.97 (m, 2H)