Реакция #42392

Уравнение реакции

(2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-{[1-(3-ethynylphenyl)cyclopropyl]amino}-3-methylbutan-2-ol dihydrochloride

Methyl 3-bromo-5-{[butyl(methyl)amino]methyl}benzoate

diisopropylethylamine

HATU

→

title compound

3-Bromo-5-{[butyl(methyl)amino]methyl}-N-((1S,2R)-1-(3,5-difluorobenzyl)-3-{[1-(3-ethynylphenyl)cyclopropyl]amino}-2-hydroxypropyl)benzamide dihydrochloride

Растворители

tetrahydrofuran methanol water

lithium hydroxide monohydrate

Условия реакции

Обработка

1. 1
   workup.ADDITIONis added (30 mg, 0.72 mmol)
2. 2
   КонцентрированиеThe solution is concentrated under reduced pressure
3. 3
   workup.DISSOLUTIONThe residue is redissolved in DMF (5 mL)
4. 4
   workup.ADDITIONare added
5. 5
   workup.STIRRINGThe reaction stirred at room temperature 16 h
6. 6
   ДругоеPurification by flash column chromatography (silica, 8% methanol/methylene chloride)

Методика

Methyl 3-bromo-5-{[butyl(methyl)amino]methyl}benzoate (113 mg, 0.36 mmol) is dissolved in 2:1:1 tetrahydrofuran/methanol/water (4 mL), and lithium hydroxide monohydrate is added (30 mg, 0.72 mmol), and the reaction stirred 16 h. The solution is concentrated under reduced pressure. The residue is redissolved in DMF (5 mL), and diisopropylethylamine (250 μL, 1.44 mmol), HATU (170 mg, 0.45 mmol), and (2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-{[1-(3-ethynylphenyl)cyclopropyl]amino}-3-methylbutan-2-ol dihydrochloride prepared as in Example SP-264 (170 mg, 0.4 mmol) are added. The reaction stirred at room temperature 16 h. Purification by flash column chromatography (silica, 8% methanol/methylene chloride) provides the title compound as the free base. The residue is dissolved in diethyl ether (3 mL) and 1N hydrochloric acid in diethyl ether (1 mL) is added. The mixture is concentrated under reduced pressure to yield the title compound. ESI MS m/z 638.2 [M+H]+.

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