N-amino-morpholine hydrochloride → 4-[(1R,2E,4R,5S,8S,12R)-4-methyl-2-morpholin-4-ylimino-6-oxo-9,13-dioxa-7-azatetracyclo[6.3.1.11,4.05,12]tridecan-7-yl]-2-(trifluoromethyl)benzonitrile

Temperature

50 °C

To a stirring solution of Example 3 (85 mg, 0.216 mmol) in pyridine (2 mL) was added. N-aminomorpholine hydrochloride (0.287 mmol, 1.5 eq). The mixture was stirred at 50° C. for 1 h. The reaction was judged completed by LCMS. The reaction mixture was cooled to room temperature. It was then diluted with EtOAc (6 ml) and extracted with 1N HCl (2×10 ml). The ethyl acetate layer was then washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The crude was purified on Isco (12 g column) 0-5% MeOH-DCM to give Example 92 (59 mg, 58%, 0.133 mmol).

1. temperatureThe reaction mixture was cooled to room temperature
2. extractionextracted with 1N HCl (2×10 ml)
3. washThe ethyl acetate layer was then washed with brine
4. dry with materialdried over anhydrous sodium sulfate
5. filtrationfiltered
6. concentrationconcentrated under reduced pressure
7. customThe crude was purified on Isco (12 g column) 0-5% MeOH-DCM

ORD record

ord-745ba4fd06154d2ea01ff42a7f25dd20

Source dataset

uspto-grants-2011_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08067582B2