Dimethylacetamide → 4-amino-N-(1-methylpiperidin-4-yl)benzamide

HRID 2234347Notes

Reaction equation

HRID 2234347 reaction equation
[NH2:1][CH:2]1[CH2:7][CH2:6][N:5]([CH3:8])[CH2:4][CH2:3]1.CCN([CH:15]([CH3:17])C)C(C)C.CN(C(ON1N=N[C:28]2[CH:29]=[CH:30][CH:31]=[N:32][C:27]1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CC(N(C)C)=[O:44]>>[NH2:32][C:27]1[CH:28]=[CH:29][C:30]([C:31]([NH:1][CH:2]2[CH2:7][CH2:6][N:5]([CH3:8])[CH2:4][CH2:3]2)=[O:44])=[CH:17][CH:15]=1

Participants

5

Reactant 4

HCID 31374Dimethylacetamide2×HCID 81531DiisopropylethylamineHCID 27375314-Amino-1-methylpiperidineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)

Product 1

HCID 433732804-amino-N-(1-methylpiperidin-4-yl)benzamideYield 72%

Procedure

p-Aminobenozoic acid (137 mg, 1 mmol), 4-amino-N-methylpiperidine (114 mg, 1 mmol) and DIPEA (522 uL, 3 mmol) were dissolved in DMA (5 mL). HATU (570 mg, 1.5 mmol) in DMA (5 mL) was added and the reaction stirred at ambient temperature for 2 h. The volatiles were removed under reduced pressure and NaHCO3 (50 mL, sat. aq.) was added. The resulting precipitate was removed by filtration and the aqueous phase neutralised with HCL (2N). The reaction mixture was then loaded onto an SCX-2 cartridge washing with copious quantities of water. The crude product was the eluted from the SCX-2 cartridge with NH3 (60 mL, 7M in MeOH). Purification by column chromatography (SiO2, eluent: 10% NH3 [7M in MeOH] in DCM) afforded the title compound (167 mg, 72%) as a solid.

Workup

  1. customThe volatiles were removed under reduced pressure and NaHCO3 (50 mL, sat. aq.)
  2. additionwas added
  3. customThe resulting precipitate was removed by filtration
  4. washwashing with copious quantities of water
  5. washeluted from the SCX-2 cartridge with NH3 (60 mL, 7M in MeOH)
  6. customPurification by column chromatography (SiO2, eluent: 10% NH3 [7M in MeOH] in DCM)

Sources & evidence

ORD record
ord-24fd16525dcc42e1b26d0459359e1cd3
Source dataset
uspto-grants-2010_05
Patent number
US07709471B2

Reaction notes

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