Triethylamine → 5-Amino-1-(4-fluorophenyl)-N-(3,3,3-trifluoro-2-{[(2-fluoroethyl)amino]methyl}-2-hydroxypropyl)-1H-pyrazole-4-carboxamide

HRID 886716Notes

Reaction equation

HRID 886716 reaction equation
[NH2:1][C:2]1[N:6]([C:7]2[CH:12]=[CH:11][C:10]([F:13])=[CH:9][CH:8]=2)[N:5]=[CH:4][C:3]=1[C:14]([NH:16][CH2:17][C:18]1([C:21]([F:24])([F:23])[F:22])[CH2:20][O:19]1)=[O:15].Cl.[F:26][CH2:27][CH2:28][NH2:29].C(N(CC)CC)C>C(#N)C>[NH2:1][C:2]1[N:6]([C:7]2[CH:12]=[CH:11][C:10]([F:13])=[CH:9][CH:8]=2)[N:5]=[CH:4][C:3]=1[C:14]([NH:16][CH2:17][C:18]([CH2:20][NH:29][CH2:28][CH2:27][F:26])([OH:19])[C:21]([F:23])([F:22])[F:24])=[O:15]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 9995Ethanamine, 2-fluoro-, hydrochlorideHCID 594874985-amino-1-(4-fluorophenyl)-N-{[2-(trifluoromethyl)-2-oxiranyl]methyl}-1H-pyrazole-4-carboxamide

Product 1

HCID 591872345-Amino-1-(4-fluorophenyl)-N-(3,3,3-trifluoro-2-{[(2-fluoroethyl)amino]methyl}-2-hydroxypropyl)-1H-pyrazole-4-carboxamideYield 128.5%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a solution of 5-amino-1-(4-fluorophenyl)-N-{[2-(trifluoromethyl)-2-oxiranyl]methyl}-1H-pyrazole-4-carboxamide (1.03 g, 3 mmol) in anhydrous acetonitrile (10 ml) was added 2-fluoroethylamine hydrochloride (650 mg, 6 mmol, ca. 90% purity) and triethylamine (0.98 ml, 7 mmol) and the resulting suspension was shaken for 4 days. It was partitioned between ethyl acetate (70 ml) and water (20 ml), washed with saturated brine (20 ml), dried over sodium sulphate and evaporated to give a gum (1.57 g). This was purified on 100 g SiO2 using the Flashmaster 2 with 0-100°/0 ethyl acetate in cyclohexane 60 minute gradient as eluent. This gave the title compound (924 mg).

Workup

  1. customIt was partitioned between ethyl acetate (70 ml) and water (20 ml)
  2. washwashed with saturated brine (20 ml)
  3. dry with materialdried over sodium sulphate
  4. customevaporated

Sources & evidence

ORD record
ord-38358a0a626447e284a8d81171153a8f
Source dataset
uspto-grants-2012_08
Patent number
US08247377B2

Reaction notes

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