Phosphorus oxychloride → Tert-butyl 4-[({4-[4-(3-bromo-4-fluorophenyl)-5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl]-1,2,5-oxadiazol-3-yl}amino)carbonyl]-4-phenylpiperidine-1-carboxylate

HRID 82727

Reaktionsgleichung

Reaktionsgleichung von HRID 82727
[NH2:1][C:2]1[C:3]([C:7]2[N:11]([C:12]3[CH:17]=[CH:16][C:15]([F:18])=[C:14]([Br:19])[CH:13]=3)[C:10](=[O:20])[O:9][N:8]=2)=[N:4][O:5][N:6]=1.[C:21]([O:25][C:26]([N:28]1[CH2:33][CH2:32][C:31]([C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=2)([C:34](O)=[O:35])[CH2:30][CH2:29]1)=[O:27])([CH3:24])([CH3:23])[CH3:22].P(Cl)(Cl)(Cl)=O>CN(C)C1C=CN=CC=1.C(#N)C>[Br:19][C:14]1[CH:13]=[C:12]([N:11]2[C:10](=[O:20])[O:9][N:8]=[C:7]2[C:3]2[C:2]([NH:1][C:34]([C:31]3([C:37]4[CH:38]=[CH:39][CH:40]=[CH:41][CH:42]=4)[CH2:32][CH2:33][N:28]([C:26]([O:25][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:27])[CH2:29][CH2:30]3)=[O:35])=[N:6][O:5][N:4]=2)[CH:17]=[CH:16][C:15]=1[F:18]

Komponenten

6

Edukt 3

HCID 24813Phosphorus oxychlorideHCID 7369171-((Tert-butoxy)carbonyl)-4-phenylpiperidine-4-carboxylic acidHCID 591483883-(4-amino-1,2,5-oxadiazol-3-yl)-4-(3-bromo-4-fluorophenyl)-1,2,4-oxadiazol-5(4H)-one

Produkt 1

HCID 67437074Tert-butyl 4-[({4-[4-(3-bromo-4-fluorophenyl)-5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl]-1,2,5-oxadiazol-3-yl}amino)carbonyl]-4-phenylpiperidine-1-carboxylate

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 142844-(Dimethylamino)pyridineKatalysatorHCID 6342AcetonitrileLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

A solution of 3-(4-amino-1,2,5-oxadiazol-3-yl)-4-(3-bromo-4-fluorophenyl)-1,2,4-oxadiazol-5(4H)-one (0.15 g, 0.44 mmol), 1-(tert-butoxycarbonyl)-4-phenylpiperidine-4-carboxylic acid (0.4 g, 1.3 mmol), and 4-dimethylaminopyridine (32 mg, 0.26 mmol) in acetonitrile (2 mL) was treated with phosphoryl chloride (0.13 mL, 1.4 mmol) and heated in the microwave at 100° C. for 10 min. The reaction mixture was concentrated and the residue was diluted with ethyl acetate (25 mL) and washed with water (25 mL) and brine (25 mL), dried with sodium sulfate, filtered, and concentrated to a crude residue which was purified by silica gel to give the coupled product, tert-butyl 4-[({4-[4-(3-bromo-4-fluorophenyl)-5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl]-1,2,5-oxadiazol-3-yl}amino)carbonyl]-4-phenylpiperidine-1-carboxylate. This material was diluted with dichloromethane (5 mL) and treated with 4.0 M HCl in 1,4-dioxane (3 mL) and stirred for 45 min. The reaction mixture was concentrated and the crude residue was purified by preparative LCMS to give the desired product (10 mg, 4%). LCMS for C22H19BrFN6O4 (M+H)+: m/z=529.0, 531.0.

Aufarbeitung

  1. concentrationThe reaction mixture was concentrated
  2. additionthe residue was diluted with ethyl acetate (25 mL)
  3. washwashed with water (25 mL) and brine (25 mL)
  4. dry with materialdried with sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated to a crude residue which
  7. customwas purified by silica gel

Quellen und Nachweise

ORD-Eintrag
ord-5960f277484f4295b2386e223e1ddadf
Quelldatensatz
uspto-grants-2014_09
Patentnummer
US08846726B2

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