Water → 5-(3,3-difluoropiperidin-1-yl)-1-(2-((trimethylsilyl)methoxy)ethyl)-1H-pyrazol-4-amine

HRID 1466653Notes

Reaction equation

[F:1][C:2]1([F:24])[CH2:7][CH2:6][CH2:5][N:4]([C:8]2[N:12]([CH2:13][CH2:14][O:15][CH2:16][Si:17]([CH3:20])([CH3:19])[CH3:18])[N:11]=[CH:10][C:9]=2[N+:21]([O-])=O)[CH2:3]1.O.[Cl-].[NH4+]>C(O)C.ClCCl.[Fe]>[F:24][C:2]1([F:1])[CH2:7][CH2:6][CH2:5][N:4]([C:8]2[N:12]([CH2:13][CH2:14][O:15][CH2:16][Si:17]([CH3:18])([CH3:20])[CH3:19])[N:11]=[CH:10][C:9]=2[NH2:21])[CH2:3]1

Participants

Conditions

Temperature: 70 °C

Procedure

To a solution of 3,3-difluoro-1-(4-nitro-1-(2-((trimethylsilyl)methoxy)ethyl)-1H-pyrazol-5-yl)piperidine (1.4 g, 3.86 mmol) in 20 mL of ethanol was added 40 mL of water, ammonium chloride (0.82 mg, 15.44 mmol), and iron powder (1.08 g, 19.3 mmol). The reaction mixture was stirred at 70° C. for 1 hour. After cooling to room temperature, the reaction mixture was diluted with dichloromethane and filtered through a celite pad, rinsing with more dichloromethane. The filtrate was extracted twice with dichloromethane, then the combined organic extracts were dried over magnesium sulfate and concentrated to afford 1.2 g (93%) of 5-(3,3-difluoropiperidin-1-yl)-1-(2-((trimethylsilyl)methoxy)ethyl)-1H-pyrazol-4-amine. LCMS (ESI) m+H=333.1; 1H NMR (400 MHz, CDCl3) δ: 7.09 (s, 1H), 5.38 (m, 2H), 3.74 (m, 6H), 2.01 (s, 1H), 1.96 (s, 2H), 1.52 (m, 2H), 0.92 (m, 2H), 0 (s, 9H).

Workup

temperatureAfter cooling to room temperature
filtrationfiltered through a celite pad
washrinsing with more dichloromethane
extractionThe filtrate was extracted twice with dichloromethane
dry with materialthe combined organic extracts were dried over magnesium sulfate
concentrationconcentrated

Sources & evidence

ORD record: ord-c03ad5a3c42a4a71a78f03ec346f20e9
Source dataset: uspto-grants-2015_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08999998B2

Reaction notes

Loading…