Реакция #164062

Уравнение реакции

mesylate

Et3N

methanesulfonyl chloride

K2CO3

NaI

3,5-Difluoro-4-[1-hydroxy-3-(1-trityl-1H-imidazol-4-yl)-propyl]benzonitrile

→

4-(6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-5-yl)-3,5-difluorobenzonitrile

Растворители

DMF

Условия реакции

Обработка

1. 1
   ДругоеThe solution is evaporated to dryness
2. 2
   workup.DISSOLUTIONdissolved in DMF (5 mL), to which
3. 3
   Температураthe mixture is heated to 90° C. for 0.5 h
4. 4
   ДругоеThe solution is then evaporated
5. 5
   workup.DISSOLUTIONdissolved in MeCN
6. 6
   Фильтрацияfiltered
7. 7
   ДругоеThe crude residue is purified via flash column chromatography (MeOH/DCM 1:99→MeOH/DCM 1:9)

Методика

3,5-Difluoro-4-[1-hydroxy-3-(1-trityl-1H-imidazol-4-yl)-propyl]benzonitrile (0.105 g, 0.21 mmol) is dissolved in DMF (5 mL) and cooled down to 0° C. To this is added Et3N (0.043 mL, 0.31 mmol) and methanesulfonyl chloride (0.019 mL, 0.25 mmol). After 2 h, LCMS showed the presence of the intermediate mesylate [MS (ESI) m/z 584.3 (M+H)]. The solution is evaporated to dryness and dissolved in DMF (5 mL), to which is added K2CO3 (0.086 g, 0.62 mmol) and NaI (0.093 g, 0.62 mmol) and the mixture is heated to 90° C. for 0.5 h. The solution is then evaporated, dissolved in MeCN and filtered. The crude residue is purified via flash column chromatography (MeOH/DCM 1:99→MeOH/DCM 1:9) to give 4-(6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-5-yl)-3,5-difluorobenzonitrile. MS (ESI) m/z 246.2 (M+H); 1H NMR (400 MHz, CDCl3) δ ppm 2.72-2.85 (m, 1H), 2.93-3.05 (m, 1H), 3.08-3.21 (m, 2H), 5.75 (app t, J=7.2 Hz, 1H), 6.79 (s, 1H), 7.18-7.41 (m, 3H).

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