تفاعل #162218

معادلة التفاعل

2-chloro-5-fluoro-N-[(3S)-1-oxaspiro[2.5]octan-7-yl]pyrimidin-4-amine

NaCN

lithium perchlorate

EtOAc

→

desired product

2-((1S,3S)-3-(2-chloro-5-fluoropyrimidin-4-ylamino)-1-hydroxy-cyclohexyl)-ethanenitrile

المذيبات

CH3CN

ظروف التفاعل

المعالجة

1. 1
   غسيلthe organic phase was washed with aqueous saturated NaHCO3 solution
2. 2
   تجفيفdried with MgSO4
3. 3
   ترشيحfiltered
4. 4
   أخرىthe solvent was removed under reduced pressure
5. 5
   أخرىThe resulting residue was purified by silica gel chromatography (EtOAc/hexanes)

الإجراء التجريبي

A suspension of 2-chloro-5-fluoro-N-[(3S)-1-oxaspiro[2.5]octan-7-yl]pyrimidin-4-amine, 49c, (0.50 g, 1.94 mmol), NaCN (0.11 g, 2.33 mmol) and lithium perchlorate (0.25 g, 2.33 mmol) in CH3CN was heated at 100° C. in a pressure tube for 3 h. The mixture was diluted into EtOAc and the organic phase was washed with aqueous saturated NaHCO3 solution, dried with MgSO4, filtered and the solvent was removed under reduced pressure. The resulting residue was purified by silica gel chromatography (EtOAc/hexanes) afforded the desired product: 1H NMR (300.0 MHz, CDCl3) δ 7.78 (d, J=2.7 Hz, 1H), 4.85 (d, J=6.6 Hz, 1H), 4.28 (qn, J=4.0 Hz, 1H), 2.45 (s, 2H), 2.16 (d, J=13.0 Hz, 1H), 2.05 (d, J=11.7 Hz, 1H), 1.80-1.71 (m, 3H), 1.46-1.28 (m, 2H) and 1.17-1.06 (m, 1H) ppm; LCMS RT=2.15 (M+H) 285.34.

المصدر