Reaktion #44483

Reaktionsgleichung

NH4OH

Trifluoroacetic acid

solution

4-[4-(5-cyano-pyridin-2-yloxymethyl)-3,3-dimethyl-2-oxo-pyrrolidin-1-yl]-azepane-1-carboxylic acid tert-butyl ester

Triphosgene

→

title compound

4-(4-{[(5-cyanopyridin-2-yl)oxy]methyl}-3,3-dimethyl-2-oxopyrrolidin-1-yl)azepane-1-carboxamide

Lösungsmittel

dichloromethane

Reaktionsbedingungen

Aufarbeitung

1. 1
   SonstigeThe solvent was evaporated in vacuo
2. 2
   workup.STIRRINGstirred for one hour
3. 3
   workup.ADDITIONwas added
4. 4
   workup.STIRRINGstirred at room temperature for one hour
5. 5
   ExtraktionThe product was extracted with dichloromethane
6. 6
   Trocknendried with MgSO4
7. 7
   Filtrationfiltered
8. 8
   Sonstigeevaporated in vacuo
9. 9
   SonstigeThe crude reaction mixture
10. 10
    Sonstigewas purified by preparative reverse phase HPLC on a Waters Symmetry C8 column (25 mm×100 mm, 7 um particle size)

Vorschrift

Trifluoroacetic acid (0.75 mL) was added to a solution of Example 2F (0.108 g, 0.24 mmoles) in dichloromethane (0.75 mL) and stirred for one hour. The solvent was evaporated in vacuo. The residue was taken in dichloromethane (1.5 mL) and cooled to −78° C. Triphosgene (24 mg, 0.08 mmoles) was added and stirred for one hour. To the reaction, NH4OH (1 mL) was added and stirred at room temperature for one hour. The product was extracted with dichloromethane, dried with MgSO4, filtered, and evaporated in vacuo. The crude reaction mixture was purified by preparative reverse phase HPLC on a Waters Symmetry C8 column (25 mm×100 mm, 7 um particle size) using a gradient of 20% to 100% acetonitrile:water (0.1% trifluoroacetic acid) over eighteen minutes at a flow rate of 40 mL/minute to provide the title compound. 1H NMR (300 MHz, CDCl3) δ ppm 8.48 (dd, J=2.33, 0.64 Hz, 1H), 7.80 (dd, J=8.66, 2.33 Hz, 1H), 6.82 (dd, J=8.66, 0.78 Hz, 1H), 5.81 (b,r, 2H), 4.50 (dd, J=10.87, 6.04 Hz, 1H), 4.36 (dd, J=10.86, 8.24 Hz, 1H), 4.03-4.19 (m, 1H), 3.16 (m, 4H), 3.46 (dd, J=9.85, 7.64 Hz, 1H), 3.08 (dd, J=9.87, 7.94 Hz, 1H), 2.45 (qd, J=7.94, 6.01 Hz, 1H), 1.43-1.82 (m, 6H), 1.24 (s, 3H), 1.06 (s, 3H). MS (APCI+) m/z 386.2 (M+H)+.

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