Diisopropylethylamine → HCID 71144214, compound

HRID 2370880Notes

Reaction equation

HRID 2370880 reaction equation
[CH3:1][O:2][C:3]1[C:8]([N+:9]([O-:11])=[O:10])=[CH:7][N:6]=[C:5]([C:12]([OH:14])=O)[CH:4]=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:12](=[O:14])[C:5]2[CH:4]=[C:3]([O:2][CH3:1])[C:8]([N+:9]([O-:11])=[O:10])=[CH:7][N:6]=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 86688001HCID 86688001, compound

Product 1

HCID 71144214HCID 71144214, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a stirred solution of 4-methoxy-5-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, Molicula, 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 petroleum ether). After completion of the reaction, water (100 mL) was added and aqueous solution was extracted with EtOAc (50 mL×3) and concentrated to give the 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 9.89 (d, J=7.2 Hz, 1H), 9.13 (s, 1H), 8.57 (d, J=4.5 Hz, 1H), 7.92 (s, 1H), 7.82 (t, J=8.7 Hz, 1H), 7.56 (t, J=4.8 Hz, 3H), 7.36 (d, J=8.4 Hz, 1H), 6.54 (d, J=6.3 Hz, 1H), 4.11 (s, 3H). MS (ESI, positive ion) m/z: 485.0 (M+H).

Workup

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

Sources & evidence

ORD record
ord-771666dab36b43fa833c576eb1118f72
Source dataset
uspto-grants-2014_04
Patent number
US08710043B2

Reaction notes

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