Diisopropylethylamine → 4-amino-N-(1-methylpiperidin-4-yl)-3-(trifluoromethoxy)benzamide

HRID 2234384Notes

Reaction equation

HRID 2234384 reaction equation
[NH2:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=O)=[CH:4][C:3]=1[O:11][C:12]([F:15])([F:14])[F:13].[NH2:16][CH:17]1[CH2:22][CH2:21][N:20]([CH3:23])[CH2:19][CH2:18]1.CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C>[NH2:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([NH:16][CH:17]2[CH2:22][CH2:21][N:20]([CH3:23])[CH2:19][CH2:18]2)=[O:8])=[CH:4][C:3]=1[O:11][C:12]([F:15])([F:14])[F:13]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 27359514-amino-3-(trifluoromethoxy)benzoic AcidHCID 27375314-Amino-1-methylpiperidineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)

Product 1

HCID 580151524-amino-N-(1-methylpiperidin-4-yl)-3-(trifluoromethoxy)benzamideYield 78%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 4-amino-3-(trifluoromethoxy)benzoic acid (Maybridge; 1.05 g, 4.75 mmol) in DMF (20 ml) was added 4-amino-1-methylpiperidine (Fluorochem; 604 mg, 5.29 mmol) followed by DIPEA (1.6 ml, 9.19 mmol) and HATU (2.06 g, 5.42 mmol). The reaction mixture was stirred at ambient temperature O/N. The reaction mixture was evaporated to dryness and the residue partitioned between DCM (75 mL) and saturated aqueous sodium bicarbonate solution (75 mL). The aqueous phase was re-extraced with DCM (50 ml) and the combined organic phases washed with brine, dried over magnesium sulphate, filtered and evaporated to give the title compound as an amber gum (1.17 g, 78%)

Workup

  1. customThe reaction mixture was evaporated to dryness
  2. customthe residue partitioned between DCM (75 mL) and saturated aqueous sodium bicarbonate solution (75 mL)
  3. washthe combined organic phases washed with brine
  4. dry with materialdried over magnesium sulphate
  5. filtrationfiltered
  6. customevaporated

Sources & evidence

ORD record
ord-4f4e3746f79f46fe81a335dc298ff525
Source dataset
uspto-grants-2010_05
Patent number
US07709471B2

Reaction notes

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