The ‘Eenie–Meenie reaction’. Displacement reactions of bisanilinopyrimidines

Author:

Pearson Stuart E.,Wood Robin

Publisher

Elsevier BV

Subject

Organic Chemistry,Drug Discovery,Biochemistry

Reference6 articles.

1. Metelation of diazines VIII metalation of 4-chloropyrimidine derivatives new synthesis of trimethoprim

2. Untersuchungen über Pyrimidine, II. Darstellung und Eigenschaften von 2.6-Dichlor-5-chlormethyl-pyrimidin

3. One-Step Hydroxy Substitution of 4,4’-Dimethoxybenzhydrol with Amides, Lactams, Carbamates, Ureas and Anilines

4. In a typical procedure, the nucleophile (0.50 mmol) and Et2O·HCl (0.50 mmol) were added to a solution of bisanilinopyrimidine 1 (0.25 mmol) in 3 ml N-methyl pyrrolidinone, and the mixture was heated to 100°C for 2 h. The reaction was monitored by TLC. The solution was cooled to room temperature and 30 ml Et2O were added, causing a solid or gum to fall out of solution. The supernatant was decanted off and the residue purified by flash chromatography (MeOH/DCM system, containing 0.5% conc. aqueous ammonia).

5. 4-Anilino-5-bromo-2-chloropyrimidine (626 mg, 2.20 mmol) and 4-aminobenzyl alcohol (246 mg, 2.00 mmol) were dissolved in n-butanol (20 ml). Ethereal HCl (1 M, 4.00 ml, 4.00 mmol) was added at room temperature, and the solution heated at 100°C for 16 h. The yellow solid, which precipitated was removed by filtration, and the filtrate was concentrated in vacuo. The crude product was twice purified by flash chromatography (firstly eluting with DCM, then eluting with 0–15% EtOAc in iso-hexane). Product (17) (270 mg, 32%) was obtained as a white solid.

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