Acetic Acid → 2-Anilino-4-(thiazol-5-yl)pyrimidine deriv. 35

HRID 1860464Notes

Reaction equation

HRID 1860464 reaction equation
[CH3:1][C:2]1[S:3][C:4]([C:8]2[CH:13]=[CH:12][N:11]=[C:10]([NH:14][C:15]3[CH:20]=[CH:19][CH:18]=[C:17]([N+:21]([O-])=O)[CH:16]=3)[N:9]=2)=[C:5]([CH3:7])[N:6]=1.CC(O)=O>COCCO.[Pd]>[CH3:1][C:2]1[S:3][C:4]([C:8]2[CH:13]=[CH:12][N:11]=[C:10]([NH:14][C:15]3[CH:20]=[CH:19][CH:18]=[C:17]([NH2:21])[CH:16]=3)[N:9]=2)=[C:5]([CH3:7])[N:6]=1

Participants

5

Reactant 2

HCID 176Acetic AcidHCID 65392934-(2,4-dimethyl-1,3-thiazol-5-yl)-N-(3-nitrophenyl)pyrimidin-2-amine

Product 1

HCID 65393002-Anilino-4-(thiazol-5-yl)pyrimidine deriv. 35

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 80192-MethoxyethanolSolvent

Procedure

To a mixture of {4-(2,4-dimethyl-thiazol-5-yl)-pyrimidin-2-yl}-(3-nitro-phenyl)-amine (3.97 mmol, 1.3 g) in 2-methoxyethanol (15 mL) was added AcOH (1 mL). The reaction mixture was stirred under N2 for 10 min. Palladium catalyst (660 mg; 10% on activated carbon) was the added and the reaction mixture was allowed to stir under H2 for 18 h. The reaction mixture was passed through Celite 521 and the precipitates were washed several times with MeOH. The filtrate was concentrated and recrystallised from MeOH/EtOAc to afford grey crystals of N-{4-(2,4-dimethyl-thiazol-5-yl)-pyrimidin-2-yl}-benzene-1,3-diamine. An aliquot of this material (500 mg) in 2-methoxylethanol was cooled on an ice bath and was treated with HCl (conc. 1 mL). Cyanamide (50% aq soln., 4 mL) was added dropwise. After completion of the addition the reaction mixture was warmed to r.t. and heated at reflux for 20 h. The reaction mixture was concentrated. The residue was diluted with EtOAc and washed with water and brine. The organic phase was evaporated and purified by chromatography, using EtOAc/MeOH (3:1, v/v) to elute the title compound. DE MALDI-TOF MS: {M+H}+=339.16 (C16H17N7S requires 339.42).

Workup

  1. additionadded
  2. stirringto stir under H2 for 18 h
  3. washthe precipitates were washed several times with MeOH
  4. concentrationThe filtrate was concentrated
  5. customrecrystallised from MeOH/EtOAc

Sources & evidence

ORD record
ord-c800aeebcbf74d98888690985de3b089
Source dataset
uspto-grants-2003_03
Patent number
US06531479B2

Reaction notes

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