Methanamine, N-methoxy-, hydrochloride (1:1) → N-methoxy-N-methyl-2-phenylamino-6-trifluoromethyl-nicotinamide

HRID 1261773Notes

Reaction equation

HRID 1261773 reaction equation
[C:1]1([NH:7][C:8]2[N:16]=[C:15]([C:17]([F:20])([F:19])[F:18])[CH:14]=[CH:13][C:9]=2[C:10]([OH:12])=O)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.Cl.[CH3:22][NH:23][O:24][CH3:25].F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1.C(N(CC)C(C)C)(C)C>CN(C)C=O.C(Cl)Cl>[CH3:25][O:24][N:23]([CH3:22])[C:10](=[O:12])[C:9]1[CH:13]=[CH:14][C:15]([C:17]([F:20])([F:19])[F:18])=[N:16][C:8]=1[NH:7][C:1]1[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1

Participants

7

Reactant 4

HCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 708171352-Phenylamino-6-trifluoromethyl-nicotinic acid

Product 1

HCID 86672055N-methoxy-N-methyl-2-phenylamino-6-trifluoromethyl-nicotinamideYield 96%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
25 °C

Procedure

A solution of 2-phenylamino-6-trifluoromethyl-nicotinic acid (6.2 g, 22.0 mmol), N,O-dimethylhydroxylamine hydrochloride (2.79 g, 28.6 mmol) and 2-(1H-benzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (13.3 g, 35.2 mmol) in N,N-dimethylformamide (120 mL) was treated with N,N-diisopropylethylamine (8.88 g, 12 mL, 68.7 mmol). The reaction mixture was stirred at 25° C. for 4 h. At this time, the reaction was diluted with methylene chloride (400 mL), washed with a saturated aqueous ammonium chloride solution (1×300 mL), a saturated aqueous sodium bicarbonate solution (1×300 mL), and a saturated aqueous sodium chloride solution (1×200 mL), dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. Flash chromatography (250 g silica column, 10-35% ethyl acetate/hexanes) afforded N-methoxy-N-methyl-2-phenylamino-6-trifluoromethyl-nicotinamide (6.86 g, 96%) as a brown oil which upon trituration with ether became a brown solid.

Workup

  1. washwashed with a saturated aqueous ammonium chloride solution (1×300 mL)
  2. dry with materiala saturated aqueous sodium bicarbonate solution (1×300 mL), and a saturated aqueous sodium chloride solution (1×200 mL), dried over anhydrous sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-40598af0a12b4532b0ffea8f68f7ded4
Source dataset
uspto-grants-2013_06
Patent number
US08471027B2

Reaction notes

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