1,2-Dichloroethane → HCID 86659194, compound

To cis-6-(trifluoromethyl)-3-piperidinecarboxylic acid (50 mg, 0.254 mmol) in THF (1.5 mL) into a 5 mL sealable vial were added molecular sieves, and the resulting mixture was stirred for 5 minutes. LiHMDS (0.888 mL, 0.888 mmol) was added dropwise, and the resulting mixture was stirred at room temperature for 2 minutes, then added 4,6-dichloro-2-(methylthio)pyrimidine (59.4 mg, 0.304 mmol). The reaction was check by LCMS after 5 minutes and observed a very clean conversion. The reaction was then stirred at room temperature for an additional 0.5 hours. Water (5 mL) was added followed by the dropwise addition of 1N HCl until the mixture became slightly acidic. The mixture was then extracted with EtOAc (3×10 mL), and the organics were combined, washed with brine, dried over MgSO4, filtered and concentrated. The crude oil was dissolved in DMF (1.5 mL), and then HOBT (78 mg, 0.507 mmol), EDC (58.3 mg, 0.304 mmol), and N-methylmorpholine (0.139 mL, 1.268 mmol) were added. The resulting mixture was stirred for 10 minutes. Benzylamine (0.033 mL, 0.304 mmol) was added, and the reaction mixture was stirred overnight at room temperature. LCMS of the reaction indicated clean conversion. To the reaction was added water (10 mL), and the resulting mixture was extracted with EtOAc (3×10 mL). The organics were then combined, washed with brine, dried over MgSO4, filtered and concentrated. The yellow oil was then purified on Biotage SNAP 10 g column gradient of 0 to 35% EtOAc in Hexanes over 30 minutes to afford the title compound (49 mg) as a clear oil. LC-MS (ES) m/z=445 [M+H]+.

1. stirringthe resulting mixture was stirred at room temperature for 2 minutes
2. customafter 5 minutes
3. stirringThe reaction was then stirred at room temperature for an additional 0.5 hours
4. extractionThe mixture was then extracted with EtOAc (3×10 mL)
5. washwashed with brine
6. dry with materialdried over MgSO4
7. filtrationfiltered
8. concentrationconcentrated
9. dissolutionThe crude oil was dissolved in DMF (1.5 mL)
10. stirringThe resulting mixture was stirred for 10 minutes
11. stirringthe reaction mixture was stirred overnight at room temperature
12. extractionthe resulting mixture was extracted with EtOAc (3×10 mL)
13. washwashed with brine
14. dry with materialdried over MgSO4
15. filtrationfiltered
16. concentrationconcentrated
17. customThe yellow oil was then purified on Biotage SNAP 10 g column gradient of 0 to 35% EtOAc in Hexanes over 30 minutes

ORD record

ord-6d07cfc591dc406a908831048b649000

Source dataset

uspto-grants-2014_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08697685B2