Dibutyl sulfide → 4-(7-Methyl-1H-indazol-5-yl)-3-pyridin-2-yl-butyric acid tert-butyl ester

HRID 2099737

Reaction equation

C(SCCCC)CCC.[N:10]1[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=1[Li].[C:17]([O:21][C:22](=[O:36])[CH:23]=[CH:24][CH2:25][C:26]1[CH:27]=[C:28]2[C:32](=[C:33]([CH3:35])[CH:34]=1)[NH:31][N:30]=[CH:29]2)([CH3:20])([CH3:19])[CH3:18]>CCOCC>[C:17]([O:21][C:22](=[O:36])[CH2:23][CH:24]([C:11]1[CH:12]=[CH:13][CH:14]=[CH:15][N:10]=1)[CH2:25][C:26]1[CH:27]=[C:28]2[C:32](=[C:33]([CH3:35])[CH:34]=1)[NH:31][N:30]=[CH:29]2)([CH3:19])([CH3:20])[CH3:18]

Participants

Conditions

Temperature: 0 °C

Procedure

To a 50-mL oven-dried flask was added di-n-butylsulfide (261 mg, 1.781 mmol, 6.4 equiv) and cuprous iodide (170 mg, 0.891 mmol, 3.2 equiv) under nitrogen. Anhydrous ether (1 mL) was added and the suspension was cooled to 0° C. before the solution of 2-pyridinyl lithium was added via canuula. A yellowish brown precipitate was formed. After stirring at 0° C. for 15 min, the cooling bath was removed and 4-(7-methyl-1H-indazol-5-yl)-but-2-enoic acid tert-butyl ester (75.8 mg, 0.278 mmol, 1.0 equiv) in anhydrous ether (1 mL) was added via syringe. The dark solution was stirred at room temperature for 40 min. LCMS indicated the formation of the desired product. The reaction mixture was then partitioned between an aqueous ammonium hydroxide/ammonium chloride solution and ethyl acetate (upon shaking, the solids gradually dissolved to a blue aqueous solution). The layers were separated and the organic layer was washed with water, brine, dried over sodium sulfate and concentrated in vacuo to an oil. Careful flash column chromatography (5% methanol in methylene chloride) afforded the desired product (10.4 mg, 11%) which was carried on without farther purification. MS (ESI) 352 (M H)+, 296 (M-tBu)+.

Workup

customTo a 50-mL oven-dried flask
additionwas added via canuula
customA yellowish brown precipitate was formed
customthe cooling bath was removed
stirringThe dark solution was stirred at room temperature for 40 min

Sources & evidence

ORD record: ord-38f34a022bf0434c8fdb08ec132e054a
Source dataset: uspto-grants-2009_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07569578B2

Linked notes

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