Diisopropylethylamine → 6-Methoxy-N-(3-(pyridin-3-yloxy)phenyl)picolinamide

HRID 1887438Notes

Reaction equation

HRID 1887438 reaction equation
[N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([O:7][C:8]2[CH:9]=[C:10]([CH:12]=[CH:13][CH:14]=2)[NH2:11])[CH:2]=1.[CH3:15][O:16][C:17]1[N:22]=[C:21]([C:23](O)=[O:24])[CH:20]=[CH:19][CH:18]=1.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1.CCN(C(C)C)C(C)C>C(Cl)Cl.O>[CH3:15][O:16][C:17]1[N:22]=[C:21]([C:23]([NH:11][C:10]2[CH:12]=[CH:13][CH:14]=[C:8]([O:7][C:3]3[CH:2]=[N:1][CH:6]=[CH:5][CH:4]=3)[CH:9]=2)=[O:24])[CH:20]=[CH:19][CH:18]=1

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 5708916-Methoxypicolinic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 212855823-(Pyridin-3-yloxy)aniline

Product 1

HCID 583375646-Methoxy-N-(3-(pyridin-3-yloxy)phenyl)picolinamideYield 93.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

Compound 5 (25 mg, 0.13 mmol, 1.0 eq), 6-methoxypicolinic acid (23 mg, 0.15 mmol, 1.1 eq), 2-(1H-7-Azabenzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (56 mg, 0.15 mmol, 1.1 eq) and DIEA (25.7 μL, 0.148 mmol, 1.10 eq) were dissolved in CH2Cl2 (1.5 mL) and stirred at rt overnight. Water was added and the layers separated. The organic layer was dried (MgSO4), filtered and concentrated in vacuo. Purification by flash chromatography on silica gel afforded 39 mg (90%) of the title compound as a yellow solid: 1H NMR (400 MHz, DMSO-d6) δ 10.26 (s, 1H), 8.41 (d, J=2.5 Hz, 1H), 8.38 (dd, J=4.4, 1.5 Hz, 1H), 7.92 (t, J=7.8 Hz, 1H), 7.70-7.69 (m, 2H), 7.65 (d, J=8.6 Hz, 1H), 7.48 (ddd, J=8.4, 2.7, 1.6 Hz, 1H), 7.45-7.39 (m, 2H), 7.08 (d, J=8.0 Hz, 1H), 6.84 (dd, J=8.1, 1.9 Hz, 1H), 4.04 (s, 3H); ES-MS [M+1]+: 322.2.

Workup

  1. customthe layers separated
  2. dry with materialThe organic layer was dried (MgSO4)
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customPurification by flash chromatography on silica gel

Sources & evidence

ORD record
ord-4985e670b37340e59ac516f19ac68d39
Source dataset
uspto-grants-2013_08
Patent number
US08501757B2

Reaction notes

Loading…