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

HRID 886704Notes

Reaction equation

HRID 886704 reaction equation
C(N(C(C)C)CC)(C)C.[NH2:10][C:11]1[N:15]([C:16]2[CH:21]=[CH:20][C:19]([F:22])=[CH:18][CH:17]=2)[N:14]=[CH:13][C:12]=1[C:23]([OH:25])=O.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[NH2:50][CH2:51][C:52]([CH2:58][N:59]([CH2:67][CH3:68])[CH2:60][C:61]1[CH:66]=[CH:65][CH:64]=[CH:63][CH:62]=1)([OH:57])[C:53]([F:56])([F:55])[F:54]>CN(C)C=O>[NH2:10][C:11]1[N:15]([C:16]2[CH:17]=[CH:18][C:19]([F:22])=[CH:20][CH:21]=2)[N:14]=[CH:13][C:12]=1[C:23]([NH:50][CH2:51][C:52]([CH2:58][N:59]([CH2:67][CH3:68])[CH2:60][C:61]1[CH:62]=[CH:63][CH:64]=[CH:65][CH:66]=1)([OH:57])[C:53]([F:56])([F:55])[F:54])=[O:25]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 52068325-amino-1-(4-fluorophenyl)-1H-pyrazole-4-carboxylic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 574449933-Amino-2-{[ethyl(phenylmethyl)amino]methyl}-1,1,1-trifluoro-2-propanol

Product 1

HCID 591872355-Amino-N-(2-{[ethyl(phenylmethyl)amino]methyl}-3,3,3-trifluoro-2-hydroxypropyl)-1-(4-fluorophenyl)-1H-pyrazole-4-carboxamideYield 150.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

Diisopropylethylamine (0.175 ml, 1 mmol) was added to a mixture of 5-amino-1-(4-fluorophenyl)-1H-pyrazole-4-carboxylic acid (0.119 g, 0.54 mmol) and 0-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (HATU) (0.205 g, 0.54 mmol) in dimethylformamide (1 ml). The resultant mixture was stirred at room temperature for 20 minutes, then a solution of 3-amino-2-{[ethyl(phenylmethyl)amino]methyl}-1,1,1-trifluoro-2-propanol (0.296 g, 1.07 mmol) in dimethylformamide (1 ml) was added. The reaction mixture was stirred at room temperature for 4 hours. The reaction mixture was partitioned between ethyl acetate (30 ml) and water (30 ml) and the separated organic phase washed with saturated aqueous sodium chloride solution, dried over magnesium sulphate, filtered and evaporated under reduced pressure. The residue was purified by chromatography on silica (10 g) using 0-100% ethyl acetate in cyclohexane gradient over 15 minutes to give the title compound (0.39 g).

Workup

  1. customThe reaction mixture was partitioned between ethyl acetate (30 ml) and water (30 ml)
  2. washthe separated organic phase washed with saturated aqueous sodium chloride solution
  3. dry with materialdried over magnesium sulphate
  4. filtrationfiltered
  5. customevaporated under reduced pressure
  6. customThe residue was purified by chromatography on silica (10 g)
  7. customover 15 minutes

Sources & evidence

ORD record
ord-4744fe6dbb1b43d588190e411e136fd5
Source dataset
uspto-grants-2012_08
Patent number
US08247377B2

Reaction notes

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