2,4-Diaminotoluene → N-(4-Methyl-3-aminophenyl)-4-(4-methylpiperazinomethyl)benzamide

HRID 1160122Notes

Reaction equation

HRID 1160122 reaction equation
[Al+3].[Cl-].[Cl-].[Cl-].[NH2:5][C:6]1[CH:7]=[C:8]([CH:10]=[CH:11][C:12]=1[CH3:13])[NH2:9].C[O:15][C:16](=O)[C:17]1[CH:22]=[CH:21][C:20]([CH2:23][N:24]2[CH2:29][CH2:28][N:27]([CH3:30])[CH2:26][CH2:25]2)=[CH:19][CH:18]=1.C(C(C(C([O-])=O)O)O)([O-])=O.[Na+].[K+].C([O-])(O)=O.[Na+]>C1(C)C=CC=CC=1.C(#N)C.COC(C)(C)C>[NH2:5][C:6]1[CH:7]=[C:8]([NH:9][C:16](=[O:15])[C:17]2[CH:18]=[CH:19][C:20]([CH2:23][N:24]3[CH2:25][CH2:26][N:27]([CH3:30])[CH2:28][CH2:29]3)=[CH:21][CH:22]=2)[CH:10]=[CH:11][C:12]=1[CH3:13]

Participants

9

Reactant 5

HCID 72612,4-DiaminotolueneHCID 516892Sodium BicarbonateHCID 782222Methyl 4-((4-methylpiperazin-1-yl)methyl)benzoateHCID 6451240Aluminum(III) ChlorideHCID 9855836Potassium sodium tartarate

Product 1

HCID 11702833N-(4-Methyl-3-aminophenyl)-4-(4-methylpiperazinomethyl)benzamideYield 81.3%

Reagents, catalysts & solvents 3

HCID 1140TolueneSolvent3×HCID 6342AcetonitrileSolventHCID 15413tert-Butyl methyl etherSolvent

Conditions

Temperature
40 °C

Procedure

A solution of AlCl3 (1000 mg, 7.5 mmol) in toluene (3 ml) and acetonitrile (3.0 ml) at 0° C. under an atmosphere of argon is treated dropwise with a solution of 3-amino-4-methyl-aniline (470 mg, 6.0 mmol) in toluene (6 ml). The resulting brown solution is heated at 40° C. A solution of 4-(4-methyl-piperazin-1-ylmethyl)-benzoic acid methyl ester (745 mg, 3.0 mmol) in toluene (2 ml) is then added dropwise over a period of 30 min. The resulting mixture is stirred at 40° C. for 8 hrs and then cooled at 0° C. An aqueous saturated potassium-sodium tartrate (30 ml) and aqueous saturated NaHCO3 (40 ml) and t-butyl methyl ether (60 ml) are added sequentially. The organic phase is separated and washed with aqueous saturated NaCl. The aqueous phases are back-extracted with t-butyl methyl ether. The organic phases are combined, dried over MgSO4 and concentrated in vacuo. Purification by flash-chromatography (SiO2, CH2Cl2/MeOH 90:10+1% aq. NH3) gives 825 mg of the title compound (75%) as yellowish crystals.

Workup

  1. temperaturecooled at 0° C
  2. customThe organic phase is separated
  3. washwashed with aqueous saturated NaCl
  4. extractionThe aqueous phases are back-extracted with t-butyl methyl ether
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated in vacuo
  7. customPurification by flash-chromatography (SiO2, CH2Cl2/MeOH 90:10+1% aq. NH3)

Sources & evidence

ORD record
ord-413ae9e04e2a427ab93744df6bd09491
Source dataset
uspto-grants-2010_10
Patent number
US07816359B2

Reaction notes

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