M-Phenylenediamine → N-(3-aminophenyl)-2-((4-carbamoylphenyl)amino)-4-(propylamino)pyrimidine-5-carboxamide

HRID 2284656Notes

Reaction equation

HRID 2284656 reaction equation
[C:1]([C:4]1[CH:9]=[CH:8][C:7]([NH:10][C:11]2[N:16]=[C:15]([NH:17][CH2:18][CH2:19][CH3:20])[C:14]([C:21]([OH:23])=O)=[CH:13][N:12]=2)=[CH:6][CH:5]=1)(=[O:3])[NH2:2].Cl.C(N=C=NCCCN(C)C)C.O.ON1C2C=CC=CC=2N=N1.C(N(CC)C(C)C)(C)C.[C:56]1([NH2:63])[CH:61]=[CH:60][CH:59]=[C:58]([NH2:62])[CH:57]=1.C(=O)([O-])O.[Na+]>C(OCC)(=O)C.CN(C)C=O>[NH2:62][C:58]1[CH:57]=[C:56]([NH:63][C:21]([C:14]2[C:15]([NH:17][CH2:18][CH2:19][CH3:20])=[N:16][C:11]([NH:10][C:7]3[CH:6]=[CH:5][C:4]([C:1](=[O:3])[NH2:2])=[CH:9][CH:8]=3)=[N:12][CH:13]=2)=[O:23])[CH:61]=[CH:60][CH:59]=1

Participants

9

Reactant 6

HCID 7935M-PhenylenediamineHCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 900517252-((4-Carbamoylphenyl)amino)-4-(propylamino)pyrimidine-5-carboxylic acid

Product 1

HCID 90051726N-(3-aminophenyl)-2-((4-carbamoylphenyl)amino)-4-(propylamino)pyrimidine-5-carboxamideYield 52.9%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To 2-((4-carbamoylphenyl)amino)-4-(propylamino)pyrimidine-5-carboxylic acid (C2, 400 mg), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (970 mg) and 1-hydroxybenzotriazole monohydrate (780 mg), N,N-dimethylformamide (5 mL) and N,N-diisopropylethylamine (430 μL) were added at room temperature, and the mixture was stirred at the same temperature for 1 hour. To the reaction mixture, 1,3-phenylenediamine (418 mg) was added at room temperature, and the mixture was stirred at the same temperature for 16 hours. To the reaction mixture, saturated aqueous sodium hydrogencarbonate and ethyl acetate were added. The organic layer was separated, washed successively with water and saturated aqueous sodium chloride, and then dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The obtained residue was purified by basic silica gel column chromatography (eluent, 95% ethyl acetate/5% methanol) to obtain N-(3-aminophenyl)-2-((4-carbamoylphenyl)amino)-4-(propylamino)pyrimidine-5-carboxamide (C6, 272 mg) as pale yellow solid.

Workup

  1. stirringthe mixture was stirred at the same temperature for 16 hours
  2. customThe organic layer was separated
  3. washwashed successively with water and saturated aqueous sodium chloride
  4. dry with materialdried over anhydrous sodium sulfate
  5. customthe solvent was evaporated under reduced pressure
  6. customThe obtained residue was purified by basic silica gel column chromatography (eluent, 95% ethyl acetate/5% methanol)

Sources & evidence

ORD record
ord-b7d95f65f588457ea2947941d05cb5b6
Source dataset
uspto-grants-2015_09
Patent number
US09145415B2

Reaction notes

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