Dibromomethane → 2-Bromo-1-(5-(4-methylthiophenyl)-1-(2-pyridyl)pyrazol-3-yl)ethan-1-one

HRID 2117972Notes

Reaction equation

HRID 2117972 reaction equation
[CH3:1][S:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[N:13]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][N:15]=3)[N:12]=[C:11]([C:20]([O:22]C)=O)[CH:10]=2)=[CH:5][CH:4]=1.[Br:24][CH2:25]Br.C[Li]>C1COCC1>[Br:24][CH2:25][C:20]([C:11]1[CH:10]=[C:9]([C:6]2[CH:5]=[CH:4][C:3]([S:2][CH3:1])=[CH:8][CH:7]=2)[N:13]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][N:15]=2)[N:12]=1)=[O:22]

Participants

5

Reactant 3

HCID 3024DibromomethaneHCID 68818768Methyl 5-(4-methylthiophenyl)-1-(2-pyridyl)pyrazole-3-carboxylateHCID 178418348HCID 178418348, compound

Product 1

HCID 875873542-Bromo-1-(5-(4-methylthiophenyl)-1-(2-pyridyl)pyrazol-3-yl)ethan-1-oneYield 69%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of methyl 5-(4-methylthiophenyl)-1-(2-pyridyl)pyrazole-3-carboxylate (prepared as described in Penning, T. D. et al. J. Med. Chem. 1997, 40, 1347-1365.; 0.39 g, 1.2 mmol) and dibromomethane (0.17 mL, 2.4 mmol) in THF (10 mL) at −78° C. under nitrogen atmosphere was added methyllithium (1.6 M in ether, 1.4 mL, 2.2 mmol). After being stirred at the same temperature for 90 minutes, the solution was quenched with aqueous sodium bicarbonate, and extracted with ethyl acetate. The combined organic extracts were dried over sodium sulfate, filtered, and concentrated. Chromatography of the residue on silica gel (2:1 EtOAc:hexane) gave the title compound (0.32 g, 69% yield) as a white foam. 1H NMR (300 MHz, CDCl3) δ 8.42-8.40 (m, 1H), 7.83 (m, 1H), 7.55-7.51 (m, 1H), 7.17-7.09 (m, 4H), 7.02 (s, 1H), 4.70 (s, 2H), 2.46 (s, 3H); LRMS (API-TIS) m/z 388 and 390 (MH+).

Workup

  1. customthe solution was quenched with aqueous sodium bicarbonate
  2. extractionextracted with ethyl acetate
  3. dry with materialThe combined organic extracts were dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-e6c1890c4203474fa88932396519dda3
Source dataset
uspto-grants-2008_10
Patent number
US07442802B2

Reaction notes

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