Sodium Hydroxide → 5-(2,2,2-Trichloroethoxycarbonyl)amino-3-t-butyl-1-(2-methylpyridin-5-yl)pyrazole

HRID 2285160Notes

Reaction equation

HRID 2285160 reaction equation
[C:1]([C:5]1[CH:6]=[C:7]([NH2:17])[N:8]([C:10]2[CH:11]=[N:12][C:13]([CH3:16])=[CH:14][CH:15]=2)[N:9]=1)([CH3:4])([CH3:3])[CH3:2].[OH-].[Na+].Cl[C:21]([O:23][CH2:24][C:25]([Cl:28])([Cl:27])[Cl:26])=[O:22]>CCOC(C)=O>[Cl:26][C:25]([Cl:28])([Cl:27])[CH2:24][O:23][C:21](=[O:22])[NH:17][C:7]1[N:8]([C:10]2[CH:11]=[N:12][C:13]([CH3:16])=[CH:14][CH:15]=2)[N:9]=[C:5]([C:1]([CH3:4])([CH3:3])[CH3:2])[CH:6]=1

Participants

5

Reactant 3

HCID 14798Sodium Hydroxide4×HCID 870632,2,2-Trichloroethyl chloroformate4×HCID 114019745-Amino-3-tert-butyl-1-(2-methylpyridine-5-yl)pyrazole

Product 1

HCID 129888165-(2,2,2-Trichloroethoxycarbonyl)amino-3-t-butyl-1-(2-methylpyridin-5-yl)pyrazoleYield 37%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

To a mixture of 5-tert-butyl-2-(6-methyl-pyridin-3-yl)-2H-pyrazol-3-ylamine (for reference procedure see for example WO2003/072569, which is incorporated herein by reference in its entirety; 833 mg, 3.62 mmol) in NaOH (1M in water, 5.4 mL, 4.4 mmol) and EtOAc (5 mL) was added 2,2,2-trichloroethyl chloroformate (548 μL, 3.98 mmol) and the reaction mixture was stirred at RT for 1 h. Additional NaOH (1M in water, 5.4 mL) and 2,2,2-trichloroethyl chloroformate (548 μL) were added and stirring at RT was continued for 1 h. Additional NaOH (1M in water, 5.4 mL) and 2,2,2-trichloroethyl chloroformate (548 μL) were added and stirring at RT was continued for 2 h. Additional NaOH (1M in water, 10.8 mL) and 2,2,2-trichloroethyl chloroformate (1.10 mL) were added and stirring at RT was continued for 24 h. The aqueous layer was extracted with EtOAc (×3) and the combined organic layers were washed with brine, dried (Na2SO4) and concentrated in vacuo. The resultant residue was purified by FCC on silica, using a gradient of 10-50% EtOAc in cyclohexane, to afford the title compound (550 mg, 37%) as a white foam. LCMS (Method 3): Rt 3.87 min, m/z 405 [MH+].

Workup

  1. stirringstirring at RT
  2. waitwas continued for 1 h
  3. stirringstirring at RT
  4. waitwas continued for 2 h
  5. stirringstirring at RT
  6. waitwas continued for 24 h
  7. extractionThe aqueous layer was extracted with EtOAc (×3)
  8. washthe combined organic layers were washed with brine
  9. dry with materialdried (Na2SO4)
  10. concentrationconcentrated in vacuo
  11. customThe resultant residue was purified by FCC on silica

Sources & evidence

ORD record
ord-70fbd45950be497290a94b4531f45eb9
Source dataset
uspto-grants-2015_09
Patent number
US09145413B2

Reaction notes

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