反应详情

Crude 2-((trans)-3-amino-4-fluoropyrrolidin-1-yl)-9-isopropyl-N-(1-methyl-1H-pyrazol-4-yl)-9H-purin-6-amine (assumed 1 mmol ca.) was partitioned between DCM (30 mL) and sat. aq. NaHCO3 (10 mL) and stirred vigorously. Acryloyl chloride (121 μL, 1.5 mmol) was added in one portion and the mixture stirred for 30 min. The mixture was then diluted with DCM (50 mL) and the organic layer was separated, dried over Na2SO4 and evaporated to give a dark residue that was subjected to chiral SFC purification to separate the two trans enantiomers (Chiralpak AD-H 21.2×250 mm 5μ column. Eluted with 30% EtOH (200 proof) in CO2 held 38° C. at 100 bar, ˜60.0 mL/min, UV detection at λ=260 nm. Peak 1(−) elutes 3.99-4.68 min. Peak 2(+) elutes 5.80-6.38 min). Yielded:

1. stirringthe mixture stirred for 30 min
2. customthe organic layer was separated
3. dry with materialdried over Na2SO4
4. customevaporated
5. customto give a dark residue that
6. customwas subjected to chiral SFC purification
7. customto separate
8. washthe two trans enantiomers (Chiralpak AD-H 21.2×250 mm 5μ column. Eluted with 30% EtOH (200 proof) in CO2 held 38° C. at 100 bar, ˜60.0 mL/min, UV detection at λ=260 nm. Peak 1(−) elutes 3.99-4.68 min. Peak 2(+) elutes 5.80-6.38 min)
9. customYielded