Methylamine → (S)-N-((3-Fluoro-4-(trifluoromethoxy)phenyl)(3-fluoropyridin-2-yl)methyl)-3-(methylamino)-4-nitrobenzamide

HRID 2370864Notes

Reaction equation

HRID 2370864 reaction equation
Cl.[F:2][C:3]1[CH:4]=[C:5]([C@@H:14]([C:16]2[C:21]([F:22])=[CH:20][CH:19]=[CH:18][N:17]=2)[NH2:15])[CH:6]=[CH:7][C:8]=1[O:9][C:10]([F:13])([F:12])[F:11].F[C:24]1[CH:25]=[C:26]([C:33]([OH:35])=O)[CH:27]=[CH:28][C:29]=1[N+:30]([O-:32])=[O:31].[CH3:36][N:37](C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.CN.C1COCC1>CN(C=O)C.O>[F:2][C:3]1[CH:4]=[C:5]([C@@H:14]([C:16]2[C:21]([F:22])=[CH:20][CH:19]=[CH:18][N:17]=2)[NH:15][C:33](=[O:35])[C:26]2[CH:27]=[CH:28][C:29]([N+:30]([O-:32])=[O:31])=[C:24]([NH:37][CH3:36])[CH:25]=2)[CH:6]=[CH:7][C:8]=1[O:9][C:10]([F:13])([F:12])[F:11]

Participants

9

Reactant 6

HCID 6329MethylamineHCID 8028TetrahydrofuranHCID 81531Diisopropylethylamine2×HCID 2306533-Fluoro-4-nitrobenzoic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 86687985(S)-(3-fluoro-4-(trifluoromethoxy)phenyl)(3-fluoropyridin-2-yl)methanamine hydrochloride2×

Product 1

HCID 71144272(S)-N-((3-Fluoro-4-(trifluoromethoxy)phenyl)(3-fluoropyridin-2-yl)methyl)-3-(methylamino)-4-nitrobenzamide

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of (S)-(3-fluoro-4-(trifluoromethoxy)phenyl)(3-fluoropyridin-2-yl)methanamine hydrochloride (1.0 g, 2.94 mmol, intermediate 6) in DMF (20 mL, Aldrich) was added 3-fluoro-4-nitrobenzenecarboxylic acid (0.543 g, 2.94 mmol, Bionet Research (A Trading Division of Key Organics Ltd)), HATU (1.228 g, 3.23 mmol, Oakwood Products, Inc.), and DIPEA (1.123 mL, 6.46 mmol, EMD Biosciences, Inc.). The resulting mixture was then stirred at room temperature for 1 h. The mixture was transferred to a pressure tube, and methylamine, 2.0M solution in THF (7.34 mL, 14.68 mmol, Aldrich) and DIPEA (1.123 mL, 6.46 mmol, EMD Biosciences, Inc.) were added. The resulting mixture was heated at 55° C. for 18 h, then cooled to room temperature. Water (150 mL) was added and the mixture was extracted with EtOAc (2×150 mL). The combined organic extracts were dried over MgSO4 and concentrated in vacuo. The residue was dissolved in DCM and the solution mixture was purified by silica gel flash column chromatography using ISCO instrument (0-100% EtOAc/hexane) to give the title compound as a yellow solid. MS (ESI, positive ion) m/z: 483 (M+H).

Workup

  1. customThe mixture was transferred to a pressure tube
  2. temperatureThe resulting mixture was heated at 55° C. for 18 h
  3. temperaturecooled to room temperature
  4. extractionthe mixture was extracted with EtOAc (2×150 mL)
  5. dry with materialThe combined organic extracts were dried over MgSO4
  6. concentrationconcentrated in vacuo
  7. dissolutionThe residue was dissolved in DCM
  8. customthe solution mixture was purified by silica gel flash column chromatography

Sources & evidence

ORD record
ord-89b99d84b9584481a1e709370fe654f8
Source dataset
uspto-grants-2014_04
Patent number
US08710043B2

Reaction notes

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