Реакция #162157

Уравнение реакции

NaOH

(1S,3S)-1-(aminomethyl)-3-(2-chloro-5-fluoropyrimidin-4-ylamino)cyclohexanol

46b

(1S,3S)-1-(aminomethyl)-3-(2-chloro-5-fluoropyrimidin-4-ylamino)cyclohexanol

DIPEA

acetyl chloride

HCl

→

N-{[(1S,3S)-3-(2-chloro-5-fluoropyrimidin-4-ylamino)-1-hydroxycyclo-hexyl]methyl}acetamide

Растворители

dichloromethane

Условия реакции

Обработка

1. 1
   ЭкстракцияThe resulting suspension was extracted with dichloromethane (50 mL)
2. 2
   ДругоеThe organic layer was dried on Na2SO4
3. 3
   Концентрированиеconcentrated in vacuo
4. 4
   Другоеto provide the crude product, which
5. 5
   Другоеwas purified by silica gel chromatography (20-100% EtOAc/hexanes gradient)

Методика

(1S,3S)-1-(aminomethyl)-3-(2-chloro-5-fluoropyrimidin-4-ylamino)cyclohexanol, 46b, (0.19 g, 0.69 mmol) was dissolved in dichloromethane (15 mL) and treated with DIPEA (1.20 mL, 6.91 mmol) and acetyl chloride (0.10 mL, 1.38 mmol). After 5 minutes, the reaction mixture was diluted into 1N HCl (30 mL), and the aqueous layer was brought to a basic pH by addition of 1N NaOH. The resulting suspension was extracted with dichloromethane (50 mL). The organic layer was dried on Na2SO4 and concentrated in vacuo to provide the crude product, which was purified by silica gel chromatography (20-100% EtOAc/hexanes gradient) to afford 195 mg of N-{[(1S,3S)-3-(2-chloro-5-fluoropyrimidin-4-ylamino)-1-hydroxycyclo-hexyl]methyl}acetamide as a white foamy solid. LCMS RT=2.82 (M+1) 317.33.

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