Diisopropylethylamine → HCID 86679986, Verbindung

Temperatur

130 °C

A mixture of 5-chloro-1-(2,2-difluoroethyl)-4-nitro-1H-pyrazole (800 mg, 3.78 mmol), 1,4-diazepan-6-ol dihydrobromide (1.58 g, 5.67 mmol) and DIPEA (2.5 mL, 14.35 mmol) in EtOH (6 mL) was heated at 130° C. in a microwave for 3 hr. The solvent was removed under reduced pressure and the residue was passed through an SCX column washing with DCM and 1:1 MeOH:DCM and MeOH and eluting with 1N ammonia in MeOH to give 1-(1-(2,2-difluoroethyl)-4-nitro-1H-pyrazol-5-yl)-1,4-diazepan-6-ol as a pale yellow gum (1.0 g). This gum (1.0 g, 3.44 mmol) was dissolved in DCM (100 mL) and treated with di-tert-butyl dicarbonate (2.25 g, 10.31 mmol) and DIPEA (2.4 mL, 13.75 mmol). The reaction mixture was stirred at room temperature for 1.5 hr and washed with saturated aqueous NaHCO3 solution (100 mL). The organic layer was separated, passed through a phase separation cartridge and the solvent removed under reduced pressure. Purification via silica gel column chromatography (0-100%) EtOAc/isohexane gave tert-butyl 4-(1-(2,2-difluoroethyl)-4-nitro-1H-pyrazol-5-yl)-6-hydroxy-1,4-diazepane-1-carboxylate as a pale green gum (46% over two steps). 1H NMR (400 MHz, CDCl3) δ 8.11 (s, 1H), 6.18 (tdd, J=55.6, 5.6, 3.2 Hz, 1H), 4.49-4.31 (m, 2H), 4.19-2.95 (m, 10H), 1.60-1.40 (m, 9H).

1. customThe solvent was removed under reduced pressure
2. washwashing with DCM and 1:1 MeOH
3. washDCM and MeOH and eluting with 1N ammonia in MeOH

ORD-Eintrag

ord-6947e6a8d4b24b78b609c92cbd20686f

Quelldatensatz

uspto-grants-2013_12

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08614206B2