Hydrochloric Acid → HCID 59504626, compound

HRID 2400533Notes

Reaction equation

Cl.[CH2:2]([C:4]1[NH:8][N:7]=[C:6]([C:9]([O:11]C)=[O:10])[C:5]=1[CH3:13])[CH3:3].CC(C)([O-])C.[K+].[CH3:20][C:21]1[CH:28]=[CH:27][C:24]([CH2:25]Br)=[CH:23][CH:22]=1.[Li+].[OH-].Cl>C(O)C.O>[CH2:2]([C:4]1[N:8]([CH2:20][C:21]2[CH:28]=[CH:27][C:24]([CH3:25])=[CH:23][CH:22]=2)[N:7]=[C:6]([C:9]([OH:11])=[O:10])[C:5]=1[CH3:13])[CH3:3]

Participants

Conditions

Temperature: 60 °C

Procedure

To a mechanically stirred solution of methyl 5-ethyl-4-methyl-1H-pyrazole-3-carboxylate hydrochloride (Step 1, 825 mg, 4.03 mmol) in dry ethanol (20 mL) was added potassium tert-butoxide (1.18 g, 10.5 mmol) and a solution of 4-methylbenzyl bromide (1.12 g, 6.05 mmol) in dry ethanol (20 mL). The reaction mixture was stirred at 60° C. over night. After being cooled to rt, LiOH (0.5N aq., 40.3 mL, 20.1 mmol) was added, and the mixture was stirred at 40° C. for additional 3 h. After being cooled to RT again, the reaction mixture was diluted with water (200 mL) and acidified with HCl (2N aq., 12.1 mL, 24.2 mmol). Extraction with dichloromethane, drying over anhydrous magnesium sulfate, filtration, evaporation of the solvent and subsequent purification by preparative HPLC afforded the title compound as a white solid (183 mg, 18%): 1H NMR (400 MHz, CDCl3) δ 7.12 (d, 2H), 7.01 (d, 2H), 5.30 (s, 2H), 2.53 (quart, 2H), 2.32 (s, 3H), 2.22 (s, 3H), 0.98 (t, 3H); ES-MS m/z 259 (MH)+; HPLC RT (Method D) 2.13 min.

Workup

temperatureAfter being cooled to rt
stirringthe mixture was stirred at 40° C. for additional 3 h
temperatureAfter being cooled to RT again
extractionExtraction with dichloromethane
dry with materialdrying over anhydrous magnesium sulfate, filtration, evaporation of the solvent and subsequent purification by preparative HPLC

Sources & evidence

ORD record: ord-86580bfd48154359b5ffbb889d691588
Source dataset: uspto-grants-2014_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08796253B2

Reaction notes

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