Diisopropylethylamine → (S)-6-(Benzyloxy)-N-((3-fluoro-4-(trifluoromethoxy)phenyl)(3-fluoropyridin-2-yl)methyl)-5-nitropicolinamide

HRID 2370839Notes

Reaction equation

HRID 2370839 reaction equation
[CH2:1]([O:8][C:9]1[N:14]=[C:13]([C:15]([OH:17])=O)[CH:12]=[CH:11][C:10]=1[N+:18]([O-:20])=[O:19])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl.[F:22][C:23]1[CH:24]=[C:25]([C@@H:34]([C:36]2[C:41]([F:42])=[CH:40][CH:39]=[CH:38][N:37]=2)[NH2:35])[CH:26]=[CH:27][C:28]=1[O:29][C:30]([F:33])([F:32])[F:31].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>[CH2:1]([O:8][C:9]1[N:14]=[C:13]([C:15]([NH:35][C@@H:34]([C:25]2[CH:26]=[CH:27][C:28]([O:29][C:30]([F:33])([F:31])[F:32])=[C:23]([F:22])[CH:24]=2)[C:36]2[C:41]([F:42])=[CH:40][CH:39]=[CH:38][N:37]=2)=[O:17])[CH:12]=[CH:11][C:10]=1[N+:18]([O-:20])=[O:19])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

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 225652636-(Benzyloxy)-5-nitropicolinic AcidHCID 86687985(S)-(3-fluoro-4-(trifluoromethoxy)phenyl)(3-fluoropyridin-2-yl)methanamine hydrochloride2×

Product 1

HCID 71144022(S)-6-(Benzyloxy)-N-((3-fluoro-4-(trifluoromethoxy)phenyl)(3-fluoropyridin-2-yl)methyl)-5-nitropicolinamide

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a stirred solution of 6-(benzyloxy)-5-nitropicolinic acid (500 mg, 0.0018 mol) in DMF (10 mL), were added (S)-(3-fluoro-4-(trifluoromethoxy)phenyl)(3-fluoropyridin-2-yl)methanamine hydrochloride (620 mg, 0.0018 mol, Intermediate 6), HATU (1 g, 0.0029 mol) and DIPEA (700 mg, 0.0054 mol). The reaction mixture was then stirred for 12 h at room temperature. Progress was monitored by TLC (100% EtOAc). After completion of reaction, water (100 mL) was added and product was extracted with EtOAc (50 mL×3) and concentrated to obtain the product which was purified by column chromatography, silica gel (100-200 mesh), using 80-100% EtOAc in petroleum ether as the eluent to afford the title compound 1H NMR (400 MHz, DMSO-d6) δ: 9.75 (d, J=7.6 Hz, 1H), 8.61-8.56 (m, 2H), 7.79 (d, J=8.4 Hz, 2H), 7.59-7.54 (m, 5H), 7.35-7.32 (m, 4H), 6.60 (d, 1H), 5.77 (s, 2H).

Workup

  1. additionwas added
  2. extractionproduct was extracted with EtOAc (50 mL×3)
  3. concentrationconcentrated
  4. customto obtain the product which
  5. customwas purified by column chromatography, silica gel (100-200 mesh)

Sources & evidence

ORD record
ord-0ec5d9f91c9c449ba430deae7afbae0c
Source dataset
uspto-grants-2014_04
Patent number
US08710043B2

Reaction notes

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