4-Amino-3-methylbenzoic acid → 4-Amino-N,3-dimethylbenzamide

HRID 1487607Notes

Reaction equation

HRID 1487607 reaction equation
[NH2:1][C:2]1[CH:10]=[CH:9][C:5]([C:6](O)=[O:7])=[CH:4][C:3]=1[CH3:11].Cl.[CH2:13]([N:15]=C=NCCCN(C)C)C.Cl.CN.C(=O)([O-])O.[Na+]>CN(C=O)C>[NH2:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([NH:15][CH3:13])=[O:7])=[CH:4][C:3]=1[CH3:11]

Participants

6

Reactant 4

HCID 755984-Amino-3-methylbenzoic acidHCID 516892Sodium BicarbonateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 6364545Methylamine hydrochloride

Product 1

HCID 167716674-Amino-N,3-dimethylbenzamideYield 18.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
25 °C

Procedure

To a solution of 4-amino-3-methylbenzoic acid (1 equiv), N1-((ethylimino)methylene)-N3,N3-dimethylpropane-1,3-diamine hydrochloride (1.2 equiv), methanamine hydrochloride (1.2 equiv) in DMF (1.3 M) was added sodium hydrogencarbonate (2 equiv). The reaction was stirred at 25° C. for 15 h. The reaction mixture was quenched with saturated aqueous sodium chloride and then washed with ethyl acetate. The organic phase was combined and washed with saturated aqueous sodium chloride. The organic layer was dried (anhydrous magnesium sulfate), filtered, and concentrated. The crude product was purified by silica gel column chromatography (0-90% ethyl acetate (with 10% 1N ammonia in MeOH) in hexane). Concentration of the desired fractions afforded the title compound (18.4% yield) as a yellow solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 2.06 (s, 3H) 2.71 (d, J=4.69 Hz, 3H) 5.33 (s, 2H) 6.56 (d, J=8.59 Hz, 1H) 7.41 (dd, J=8.39, 2.15 Hz, 1H) 7.45 (s, 1H) 7.87-7.99 (m, 1H); MS (ESI) m/z 165.4 [M+1]+.

Workup

  1. customThe reaction mixture was quenched with saturated aqueous sodium chloride
  2. washwashed with ethyl acetate
  3. washwashed with saturated aqueous sodium chloride
  4. dry with materialThe organic layer was dried (anhydrous magnesium sulfate)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude product was purified by silica gel column chromatography (0-90% ethyl acetate (with 10% 1N ammonia in MeOH) in hexane)

Sources & evidence

ORD record
ord-b4e19f0b311f4929864d24b568355318
Source dataset
uspto-grants-2016_08
Patent number
US09428509B2

Reaction notes

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