Diisopropylethylamine → (S)-N-((3-Fluoro-4-(trifluoromethoxy)phenyl)(3-fluoropyridin-2-yl)methyl)-5-methoxy-4-nitropicolinamide

HRID 2370872Notes

Reaction equation

HRID 2370872 reaction equation
[CH3:1][O:2][C:3]1[C:4]([N+:12]([O-:14])=[O:13])=[CH:5][C:6]([C:9]([OH:11])=O)=[N:7][CH:8]=1.Cl.[F:16][C:17]1[CH:18]=[C:19]([C@@H:28]([C:30]2[C:35]([F:36])=[CH:34][CH:33]=[CH:32][N:31]=2)[NH2:29])[CH:20]=[CH:21][C:22]=1[O:23][C:24]([F:27])([F:26])[F:25].CN(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(C=O)C.O.CCOC(C)=O>[F:16][C:17]1[CH:18]=[C:19]([C@@H:28]([C:30]2[C:35]([F:36])=[CH:34][CH:33]=[CH:32][N:31]=2)[NH:29][C:9](=[O:11])[C:6]2[CH:5]=[C:4]([N+:12]([O-:14])=[O:13])[C:3]([O:2][CH3:1])=[CH:8][N:7]=2)[CH:20]=[CH:21][C:22]=1[O:23][C:24]([F:27])([F:26])[F:25]

Participants

8

Reactant 4

HCID 81531DiisopropylethylamineHCID 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×HCID 866880005-Methoxy-4-nitropicolinic Acid

Product 1

HCID 71144521(S)-N-((3-Fluoro-4-(trifluoromethoxy)phenyl)(3-fluoropyridin-2-yl)methyl)-5-methoxy-4-nitropicolinamide

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a stirred solution of 5-methoxy-4-nitropicolinic acid (1 g, 0.005 mol) in DMF (10 mL) were added (S)-(3-fluoro-4-(trifluoromethoxy)phenyl)(3-fluoropyridin-2-yl)methanamine hydrochloride (1.8 g, 0.0055 mol, Intermediate 6), HATU (2.8 g, 0.0075 mol, molekula, India) and DIPEA (2.4 g, 0.02 mol, Aldrich). The reaction mixture was stirred for 12 h at rt. The reaction progress was monitored by TLC (50% EtOAc in pet ether). After completion of reaction, water (10 mL) was added and product was extracted with EtOAc (50 mL×3) and concentrated to get initial product. The product thus obtained was purified by column chromatography, silica gel (60-120 mesh), using 80-100% EtOAc in petroleum ether as the eluent to give the title compound. 1H NMR (400 MHz, DMSO-d6) δ ppm 9.74 (d, J=7.6 Hz, 1H), 8.94 (s, 1H), 8.56 (d, J=4.8 Hz, 1H), 8.38 (s, 1H), 7.82 (t, J=8.8 Hz, 1H), 7.57-7.53 (m, 3H), 7.35 (d, J=8.8 Hz, 1H), 6.55 (d, J=7.2 Hz, 1H), 4.16 (s, 3H). MS (ESI, positive ion) m/z: 485.1 (M+H).

Workup

  1. additionwas added
  2. extractionproduct was extracted with EtOAc (50 mL×3)
  3. concentrationconcentrated
  4. customto get initial product
  5. customThe product thus obtained
  6. customwas purified by column chromatography, silica gel (60-120 mesh)

Sources & evidence

ORD record
ord-c4e799565649477aa6273a27cd23f9f6
Source dataset
uspto-grants-2014_04
Patent number
US08710043B2

Reaction notes

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