Toluene → HCID 67271776, compound

HRID 1696587Notes

Reaction equation

HRID 1696587 reaction equation
[NH2:1][C:2]1[N:6]([C:7]2[CH:12]=[CH:11][C:10]([CH2:13][C:14]([O:16][CH2:17][CH3:18])=[O:15])=[CH:9][CH:8]=2)[N:5]=[C:4]([C:19]2[S:20][CH:21]=[CH:22][CH:23]=2)[CH:3]=1.[CH3:24][Si]([N-][Si](C)(C)C)(C)C.[K+].C1(C)C=CC=CC=1.CI>C1COCC1>[NH2:1][C:2]1[N:6]([C:7]2[CH:8]=[CH:9][C:10]([CH:13]([CH3:24])[C:14]([O:16][CH2:17][CH3:18])=[O:15])=[CH:11][CH:12]=2)[N:5]=[C:4]([C:19]2[S:20][CH:21]=[CH:22][CH:23]=2)[CH:3]=1

Participants

6

Reactant 4

HCID 1140TolueneHCID 6328Methyl iodideHCID 3251421Potassium bis(trimethylsilyl)amideHCID 58851563HCID 58851563, compound

Product 1

HCID 67271776HCID 67271776, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

To a solution of ethyl 2-(4-(5-amino-3-(thiophen-2-yl)-1H-pyrazol-1-yl)phenyl)acetate (0.244 g, 0.745 mmol) in THF (7.5 ml), thoroughly cooled to −78° C., was added KHMDS in PhMe (1.79 ml, 0.894 mmol, 0.500 M). The resulting very dark mixture was stirred at −78° C. for 1 h and then treated with MeI (0.056 ml, 0.894 mmol). The reaction was stirred with gradual warming to RT overnight. The completed reaction was quenched by addition of 3M HCl, diluted with EtOAc and the layers separated. The aqueous was extracted with EtOAc (2×) and the combined organics were washed with satd. NaHCO3 (1×), brine (1×), dried (MgSO4), filtered, and concentrated to yield ethyl 2-(4-(5-amino-3-(thiophen-2-yl)-1H-pyrazol-1-yl)phenyl)propanoate (0.25 g) of crude which was used without further purification in the next reaction. MS (ESI) m/z: 342.3 (M+H+).

Workup

  1. stirringThe reaction was stirred
  2. temperaturewith gradual warming to RT overnight
  3. customThe completed reaction
  4. customwas quenched by addition of 3M HCl
  5. additiondiluted with EtOAc
  6. customthe layers separated
  7. extractionThe aqueous was extracted with EtOAc (2×)
  8. washthe combined organics were washed with satd
  9. dry with materialNaHCO3 (1×), brine (1×), dried (MgSO4)
  10. filtrationfiltered
  11. concentrationconcentrated

Sources & evidence

ORD record
ord-8f4603e6069141b09ec396d9e98d6d53
Source dataset
uspto-grants-2012_04
Patent number
US08163756B2

Reaction notes

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