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

HRID 1670187Notes

Reaction equation

HRID 1670187 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-f45e30e5fb5e41eaa25e68c3e6d557ae
Source dataset
uspto-grants-2011_08
Patent number
US07989477B2

Reaction notes

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