Cesium carbonate → trans 6-[(2-{2-[1-(5-Chloropyrimidin-2-yl)piperidin-4-yl]cyclopropyl}ethyl)amino]-2-methylpyrimidine-4-carbonitrile

2-{2-[1-(5-chloropyrimidin-2-yl)piperidin-4-yl]cyclopropyl}ethanamine from Example 60 Step 1 (50 mg, 0.178 mmol) was in 0.5 mL DMF. Cs2CO3 (290 mg, 0.890 mmol) was added. Reaction mixture was stirred at room temperature for 10 min before cooled to 0° C. in ice bath. 6-chloro-2-methylpyrimidine-4-carbonitrile from Example 5 step 4 (30.1 mg, 0.196 mmol) in 0.3 mL DMF was added via syringe. Reaction was stirred at 0° C. in ice bath for 2 hours. The mixture was quenched with ice water and aqueous phase was further extracted with ethyl acetate for 3 times. The combined organic layers were washed with water and brine, then dried over Na2SO4 and concentrated. The residue was purified by column chromatography eluting with 30% Ethyl acetate/hexane with 0.5% 2M NH3-MeOH to give the titled compound.

1. customReaction mixture
2. temperaturebefore cooled to 0° C. in ice bath
3. customReaction
4. stirringwas stirred at 0° C. in ice bath for 2 hours
5. customThe mixture was quenched with ice water and aqueous phase
6. extractionwas further extracted with ethyl acetate for 3 times
7. washThe combined organic layers were washed with water and brine
8. dry with materialdried over Na2SO4
9. concentrationconcentrated
10. customThe residue was purified by column chromatography
11. washeluting with 30% Ethyl acetate/hexane with 0.5% 2M NH3-MeOH

ORDレコード

ord-6b2a1b58dfac4386964c308acafc69be

出典データセット

uspto-grants-2013_10

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08552022B2