Triethylamine → 1-[(4-Methoxy)phenyl]-3-[(2-hydroxy)ethylamino]-1H-pyrazole

HRID 610150Notes

Reaction equation

HRID 610150 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([N:9]2[CH:13]=[CH:12][C:11]([NH:14][CH2:15][C:16](OC)=[O:17])=[N:10]2)=[CH:5][CH:4]=1.C(N(CC)CC)C.ClC(OCC)=O.[BH4-].[Na+]>O1CCCC1.O>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([N:9]2[CH:13]=[CH:12][C:11]([NH:14][CH2:15][CH2:16][OH:17])=[N:10]2)=[CH:7][CH:8]=1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 10928Ethyl chloroformateHCID 4311764Sodium borohydrideHCID 865879801-[(4-Methoxy)phenyl]-3-[(methoxycarbonyl)methylamino]-1H-pyrazole

Product 1

HCID 865879811-[(4-Methoxy)phenyl]-3-[(2-hydroxy)ethylamino]-1H-pyrazoleYield 55.6%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 1-[(4-methoxy)phenyl]-3-[N-glycyl]-1H-pyrazole-5-[(2'-aminosulfonyl-[1,1']-biphen-4-yl)carboxyamide (0.14 g, 0.27 mmol) in tetrahydrofuran at -20° C. was added triethylamine (0.038 mL, 0.27 mmol) and ethyl chloroformate (0.026 mL, 0.27 mmol). This mixture was stirred for 30 min and then there was added sodium borohydride (20 mg, 0.54 mmol) in a minimal amount of water. The reaction mixture was stirred with slow warming to room temperature for 1 h and then was quenched with 10% aq HCl. After diluting with ethyl acetate, the organics were washed with brine, dried (MgSO4) and concentrated in vacuo. The residue was purified by prep HPLC (C18 reverse phase column, elution with a H2O/CH3CN gradient with 0.5% TFA) and lyophilized to afford 35 mg (26%) of the title compound as a white powder. LRMS (ES+): 507.9 (M+H)+.

Workup

  1. stirringThe reaction mixture was stirred
  2. customwas quenched with 10% aq HCl
  3. additionAfter diluting with ethyl acetate
  4. washthe organics were washed with brine
  5. dry with materialdried (MgSO4)
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by prep HPLC (
  8. washC18 reverse phase column, elution with a H2O/CH3CN gradient with 0.5% TFA) and

Sources & evidence

ORD record
ord-5c27ac8a9f184653954a3b2bff202b90
Source dataset
uspto-grants-1999_12
Patent number
US05998424

Reaction notes

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