Diisopropylethylamine → N-(4-Fluorophenyl)-N-(4-(pyridin-4-yloxy)phenyl)malonamide

HRID 2373935Notes

Reaction equation

HRID 2373935 reaction equation
N[C:2]1[CH:14]=[CH:13][C:5]([O:6][C:7]2[CH:12]=[CH:11][N:10]=[CH:9][CH:8]=2)=[CH:4][CH:3]=1.[F:15][C:16]1[CH:21]=[CH:20][C:19]([NH:22][C:23](=[O:28])[CH2:24][C:25]([OH:27])=O)=[CH:18][CH:17]=1.CC[N:31](C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F>CN(C=O)C>[F:15][C:16]1[CH:17]=[CH:18][C:19]([N:22]([C:2]2[CH:3]=[CH:4][C:5]([O:6][C:7]3[CH:12]=[CH:11][N:10]=[CH:9][CH:8]=3)=[CH:13][CH:14]=2)[C:23](=[O:28])[CH2:24][C:25]([NH2:31])=[O:27])=[CH:20][CH:21]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 43418433-(4-Fluorophenylamino)-3-oxopropanoic acidHCID 115645894-(Pyridin-4-yloxy)aniline

Product 1

HCID 11610278N-(4-Fluorophenyl)-N-(4-(pyridin-4-yloxy)phenyl)malonamideYield 76.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of 4-(4-aminophenoxy)pyridine (93 mg, 0.50 mmol) in DMF was treated with 3-(4-fluorophenylamino)-3-oxopropanoic acid (99 mg, 0.50 mmol), DIPEA (113 μL, 0.65 mmol) and TBTU (209 mg, 0.65 mmol) and the mixture was stirred at RT for 2 h. The mixture was concentrated to remove the DMF and the residue partitioned between EtOAc and saturated sodium bicarbonate solution. The EtOAc phase was washed with saturated sodium bicarbonate solution, brine, dried (MgSO4) and concentrated to give the title compound as an off-white foam (140 mg, 76%). 1H NMR (DMSO-d6) δ 10.30 (s, 1H), 10.24 (s, 1H), 8.43 (dd, 2H, J=5.5, 1.5 Hz), 7.70 (d, 2H, J=9.1 Hz), 7.63-7.60 (m, 2H), 7.17-7.14 (m, 4H), 6.89 (dd, 2H, J=5.5, 1.5 Hz), 3.46 (s, 2H); MS(ESI+) m/z 365.9 (M+H)+.

Workup

  1. concentrationThe mixture was concentrated
  2. customto remove the DMF
  3. customthe residue partitioned between EtOAc and saturated sodium bicarbonate solution
  4. washThe EtOAc phase was washed with saturated sodium bicarbonate solution, brine
  5. dry with materialdried (MgSO4)
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-e6a1bc5a3ce1475083ea543731a23574
Source dataset
uspto-grants-2008_12
Patent number
US07459562B2

Reaction notes

Loading…