Azidotrimethylsilane → HCID 89456729, compound

Temperature

60 °C

To as solution of (Z)-tert-butyl 3-oxo-2,3,6,7-tetrahydro-1H-azepine-1-carboxylate (2.0 g, 9.5 mmol) in acetonitrile (3 mL), was added trimethylsilyl azide (3.76 mL, 28.4 mmol) followed by AMBERLITE® IRA 900F resin (loading: 2-3 mmolg-1, 2.4 g) and the resulting mixture was heated at 60° C. behind a blast shield for 16 hr. After cooling to room temperature, the solution was filtered washing the resin with acetonitrile and the filtrate was concentrated under reduced pressure (temperature of bath<40° C.) to give tert-butyl 5-azido-3-oxoazepane-1-carboxylate as a yellow liquid (2.21 g). To a solution of the azide (2.2 g, 8.70 mmol) in THF/water (1/1, 40 mL), was added portionwise NaBH4 (0.82 mg, 21.8 mmol) and the mixture was stirred at room temperature for 2 hr. The mixture was diluted with water (100 mL) and extracted with EtOAc (100 mL). The organic layer was separated, dried over MgSO4 and the solvent removed under reduced pressure. Purification via silica gel column chromatography (0-60% EtOAc/isohexane) gave tert-butyl 5-azido-3-hydroxyazepane-1-carboxylate as an oil (2.01 g). To a solution of this oil (2.0 g, 7.8 mmol) in MeOH (20 mL), was added HCl (4 M in 1,4-dioxane, 43 mL, 173 mmol) and the solution was stirred at room temperature for 16 hr. The solvents were removed under reduced pressure and the crude residue was dissolved in MeOH and passed through an SCX column, washing with MeOH and eluting with 7 N ammonia in MeOH to give 5-azidoazepan-3-ol as a yellow oil. To this oil in dry DMSO (20 mL) was added potassium fluoride (1.68 g, 28.9 mmol) and 5-chloro-1-methyl-4-nitro-1H-pyrazole from Example 1 (1.17 g, 7.2 mmol) and the mixture heated at 65° C. for 16 hr. The mixture was diluted with water (300 mL) and extracted with EtOAc (2×50 mL). The combined organic layers were washed with water (3×20 mL), separated, dried over MgSO4 and the solvents removed under reduced pressure. Purification via silica gel column chromatography (0-30% EtOAc/isohexane) gave 5-azido-1-(1-methyl-4-nitro-1H-pyrazol-5-yl)azepan-3-ol as a viscous yellow oil (1.9 g, 72% over four steps). 1H NMR (400 MHz, CDCl3) δ 8.06 and 8.02 (2s, 1H), 4.15-3.97 (m, 2H), 3.95-3.83 (m, 4H), 3.58-3.46 (m, 1H), 3.39-3.16 (m, 3H), 2.29-1.91 (m, 4H).

1. temperatureAfter cooling to room temperature
2. filtrationthe solution was filtered
3. washwashing the resin with acetonitrile
4. concentrationthe filtrate was concentrated under reduced pressure (temperature of bath<40° C.)

ORD record

ord-62af78045ffa43ce9a45989dcf34049b

Source dataset

uspto-grants-2013_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08614206B2