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Trifluoroacetic anhydride → Tert-butyl 4-(3-cyano-1-(4-(methylsulfonyl)phenyl)-6-oxo-1,6-dihydropyridazin-4-yloxy)piperidine-1-carboxylate

HRID 386564
Notizen
Druckvorschau

Reaktionsgleichung

Reaktionsgleichung von HRID 386564
[C:1]([C:4]1[C:9]([O:10][CH:11]2[CH2:16][CH2:15][N:14]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:13][CH2:12]2)=[CH:8][C:7](=[O:24])[N:6]([C:25]2[CH:30]=[CH:29][C:28]([S:31]([CH3:34])(=[O:33])=[O:32])=[CH:27][CH:26]=2)[N:5]=1)(=O)[NH2:2].C(OC(C(F)(F)F)=O)(C(F)(F)F)=O>C1COCC1>[C:1]([C:4]1[C:9]([O:10][CH:11]2[CH2:16][CH2:15][N:14]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:13][CH2:12]2)=[CH:8][C:7](=[O:24])[N:6]([C:25]2[CH:30]=[CH:29][C:28]([S:31]([CH3:34])(=[O:32])=[O:33])=[CH:27][CH:26]=2)[N:5]=1)#[N:2]
KomponentenVersuchsvorschriftAufarbeitungQuellen und NachweiseNotizen zur Reaktion

Komponenten

4

Edukt 2

HCID 9845Trifluoroacetic anhydrideHCID 67446737Tert-butyl 4-(3-carbamoyl-1-(4-(methylsulfonyl)phenyl)-6-oxo-1,6-dihydropyridazin-4-yloxy)piperidine-1-carboxylate

Produkt 1

HCID 44620998Tert-butyl 4-(3-cyano-1-(4-(methylsulfonyl)phenyl)-6-oxo-1,6-dihydropyridazin-4-yloxy)piperidine-1-carboxylateAusbeute 95,7 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028Tetrahydrofuran
Lösungsmittel

Versuchsvorschrift

To a stirring solution of tert-butyl 4-(3-carbamoyl-1-(4-(methylsulfonyl)phenyl)-6-oxo-1,6-dihydropyridazin-4-yloxy)piperidine-1-carboxylate (985 mg, 2.0 mmol) in THF (50 mL) at room temperature under argon was added TEA (405 mg, 4.0 mmol), and was followed by addition of TFAA (840 mg, 4.0 mmol). The resulting reaction mixture was stirred at room temperature overnight. The solvent was removed in vacuo. The crude product was dissolved in a small amount of DCM (˜5 ml) and loaded onto a 40 g ISCO silica gel column which was eluted with a 20 min gradient from 20% to 100% EtOAc/Hexanes. 908 mg (91%) of tert-butyl 4-(3-cyano-1-(4-(methylsulfonyl)phenyl)-6-oxo-1,6-dihydropyridazin-4-yloxy)piperidine-1-carboxylate was obtained as a white solid. 1H NMR (400 MHz, CDCl3) δ ppm 1.43-1.51 (m, 9H) 1.81-1.95 (m, 2H) 1.95-2.09 (m, 2H) 3.27-3.57 (m, 2H) 3.57-3.88 (m, 2H) 4.38-4.81 (m, 1H) 6.29 (s, 1H) 7.83 (d, J=8.35 Hz, 1H) 8.20 (dd, J=8.57, 2.42 Hz, 1H) 9.04 (d, J=2.64 Hz, 1H). MS (ESI) 419 (M+H-tBu).

Aufarbeitung

  1. customThe resulting reaction mixture
  2. customThe solvent was removed in vacuo
  3. dissolutionThe crude product was dissolved in a small amount of DCM (˜5 ml)
  4. washwas eluted with a 20 min gradient from 20% to 100% EtOAc/Hexanes

Quellen und Nachweise

ORD-Eintrag
ord-e2827b90aa92410f846efd945264d1fd
Quelldatensatz
uspto-grants-2013_02
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US08372837B2

Notizen zur Reaktion

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