4-Methylmorpholine → tert-Butyl 1,1,1-trifluoro-3-oxo-3-(2-(phenylcarbamoyl)-1H-pyrrol-1-ylamino)propan-2-ylcarbamate

HRID 525005Notes

Reaction equation

HRID 525005 reaction equation
[NH2:1][N:2]1[CH:6]=[CH:5][CH:4]=[C:3]1[C:7]([NH:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)=[O:8].[C:16]([O:20][C:21]([NH:23][CH:24]([C:28]([F:31])([F:30])[F:29])[C:25](O)=[O:26])=[O:22])([CH3:19])([CH3:18])[CH3:17].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CN1CCOCC1>ClCCl>[F:29][C:28]([F:30])([F:31])[CH:24]([NH:23][C:21](=[O:22])[O:20][C:16]([CH3:17])([CH3:19])[CH3:18])[C:25](=[O:26])[NH:1][N:2]1[CH:6]=[CH:5][CH:4]=[C:3]1[C:7](=[O:8])[NH:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1

Participants

6

Reactant 4

HCID 79724-MethylmorpholineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 534037822-{[(Tert-butoxy)carbonyl]amino}-3,3,3-trifluoropropanoic acidHCID 709224541-amino-N-phenyl-1H-pyrrole-2-carboxamide

Product 1

HCID 86722026tert-Butyl 1,1,1-trifluoro-3-oxo-3-(2-(phenylcarbamoyl)-1H-pyrrol-1-ylamino)propan-2-ylcarbamateYield 47%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

1-Amino-N-phenyl-1H-pyrrole-2-carboxamide (570 mg, 2.83 mmol), 2-(tert-butoxycarbonylamino)-3,3,3-trifluoropropanoic acid (826 mg, 3.40 mmol), HATU (1.29 g, 3.40 mmol) and N-methylmorpholine (685 μl, 6.23 mmol) were suspended in 20 mL of dichloromethane and stirred overnight. The reaction mixture was diluted with more dichloromethane and the solution was washed with water and brine, dried over magnesium sulphate, filtered and the solvent was removed in vacuum. The product was purified by reverse phase chromatography (C-18 silica from Waters®, water/1:1 acetonitrile-methanol as eluents [0.1% v/v formic acid buffered] 0% to 100%) to obtain the title compound in a 47% yield (562 mg) as a white solid.

Workup

  1. washthe solution was washed with water and brine
  2. dry with materialdried over magnesium sulphate
  3. filtrationfiltered
  4. customthe solvent was removed in vacuum
  5. customThe product was purified by reverse phase chromatography (C-18 silica from Waters®, water/1:1 acetonitrile-methanol as eluents [0.1% v/v formic acid

Sources & evidence

ORD record
ord-b05de11885a64b50acbc1d05ef9b2033
Source dataset
uspto-grants-2016_05
Patent number
US09340547B2

Reaction notes

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