4-Aminobenzoic Acid → 4-amino-N-methyl-N-(2-pyridin-2-ylethyl)benzamide

HRID 17833

Reaction equation

HRID 17833 reaction equation
[NH2:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=O)=[CH:4][CH:3]=1.[CH3:11][NH:12][CH2:13][CH2:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][N:16]=1.CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C>[NH2:1][C:2]1[CH:3]=[CH:4][C:5]([C:6]([N:12]([CH3:11])[CH2:13][CH2:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][N:16]=2)=[O:8])=[CH:9][CH:10]=1

Participants

6

Reactant 4

HCID 9784-Aminobenzoic AcidHCID 2366BetahistineHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)

Product 1

HCID 283991514-amino-N-methyl-N-(2-pyridin-2-ylethyl)benzamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

p-Aminobenzoic acid (1 g, 0.0073 mol) was dissolved in DMF (15 ml), methyl-(2-pyridin-2-yl-ethyl)amine (5 ml, 5 eq) was added, followed by DIPEA (1.91 ml, 1.5 eq), and HATU (4.1 g, 1.5 eq). After stirring for 3 h, TLC showed complete consumption of starting material. Water was added and the mixture extracted with CH2Cl2, the organic extracts were washed with NaHCO3 (sat), NH4Cl (sat), dried (MgSO4), concentrated under reduced pressure, and purified by flash chromatography (SiO2, EtOAc-EtOAc/MeOH 95:5) to give 1.43 g of 4-amino-N-methyl-N-(2-pyridin-2-ylethyl)benzamide. Step B: Preparation 1B (100 mg, 0.371 mmol) and the product of step A (142 mg, 1.5 eq) were dissolved in DMF (2 ml), potassium tert-butoxide (91 mg, 2.2 eq) was added and the mixture allowed to stir overnight. Water was added and the mixture extracted with EtOAc, dried (MgSO4), concentrated under reduced pressure, and the residue purified by flash chromatography (SiO2, hexane-EtOAc) to give 56 mg of the title compound. LCMS: MH+=489.3.

Workup

  1. customconsumption of starting material
  2. additionWater was added
  3. extractionthe mixture extracted with CH2Cl2
  4. washthe organic extracts were washed with NaHCO3 (sat), NH4Cl (sat)
  5. dry with materialdried (MgSO4)
  6. concentrationconcentrated under reduced pressure
  7. custompurified by flash chromatography (SiO2, EtOAc-EtOAc/MeOH 95:5)

Sources & evidence

ORD record
ord-9278e2e1590149b49e3719679cf90bb5
Source dataset
uspto-grants-2010_06
Patent number
US07741318B2

Linked notes

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