Carbon Tetrachloride → (S)-3-(3-(4-(5-amino-1,3,4-thiadiazol-2-yl)phenyl)pyrazolo[1,5-a]pyrimidin-5-yl)-4-isopropyloxazolidin-2-one

HRID 539002Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 539002
[CH:1]([C@H:4]1[CH2:8][O:7][C:6](=[O:9])[N:5]1[C:10]1[CH:15]=[CH:14][N:13]2[N:16]=[CH:17][C:18]([C:19]3[CH:31]=[CH:30][C:22]([C:23]([NH:25][NH:26][C:27](=[S:29])[NH2:28])=O)=[CH:21][CH:20]=3)=[C:12]2[N:11]=1)([CH3:3])[CH3:2].C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C(N(CC)CC)C.C(Cl)(Cl)(Cl)Cl>ClCCl.CCOC(C)=O>[NH2:28][C:27]1[S:29][C:23]([C:22]2[CH:30]=[CH:31][C:19]([C:18]3[CH:17]=[N:16][N:13]4[CH:14]=[CH:15][C:10]([N:5]5[C@@H:4]([CH:1]([CH3:3])[CH3:2])[CH2:8][O:7][C:6]5=[O:9])=[N:11][C:12]=34)=[CH:20][CH:21]=2)=[N:25][N:26]=1

Komponenten

7

Edukt 4

HCID 5943Carbon TetrachlorideHCID 8471TriethylamineHCID 11776TriphenylphosphineHCID 86667822(S)-2-(4-(5-(4-isopropyl-2-oxooxazolidin-3-yl)pyrazolo[1,5-a]pyrimidin-3-yl)benzoyl)hydrazinecarbothioamide

Produkt 1

HCID 67034573(S)-3-(3-(4-(5-amino-1,3,4-thiadiazol-2-yl)phenyl)pyrazolo[1,5-a]pyrimidin-5-yl)-4-isopropyloxazolidin-2-oneAusbeute 7,4 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6344DichloromethaneLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Reaktionsbedingungen

Temperatur
50 °C

Versuchsvorschrift

To a solution of (S)-2-(4-(5-(4-isopropyl-2-oxooxazolidin-3-yl)pyrazolo[1,5-a]pyrimidin-3-yl)benzoyl)hydrazinecarbothioamide (20.2 mg, 0.029 mmol) in dichloromethane (3 ml) was added PPh3 (22.7 mg, 0.087 mmol), triethylamine (32 μL, 0.231 mmol), and CCl4 (13.3 mg, 0.087 mmol). The reaction mixture was heated to 50° C. for 3 hours. After cooling to ambient temperature the reaction mixture was dissolved in EtOAc, washed with water then brine, dried over MgSO4, and concentrated under reduced pressure. The crude was purified by silica gel flash column chromatography (0-5% 7N NH3-MeOH in dichloromethane). The product was then subjected to preparative plate chromatography (10% MeOH in dichloromethane) to afford 0.9 mg (7%) of (S)-3-(3-(4-(5-amino-1,3,4-thiadiazol-2-yl)phenyl)pyrazolo[1,5-a]pyrimidin-5-yl)-4-isopropyloxazolidin-2-one. 1H NMR (400 MHz, CDCl3) δ 8.60 (d, 1H), 8.42 (s, 1H), 8.08 (m, 3H), 7.76 (d, 2H), 4.95 (m, 1H), 4.46 (m, 2H), 2.85 (m, 1H), 1.10 (d, 3H), 0.95 (d, 3H); LCMS (APCI+) m/z 422.5 [M+H]+.

Aufarbeitung

  1. temperatureAfter cooling to ambient temperature the reaction mixture
  2. washwashed with water
  3. dry with materialbrine, dried over MgSO4
  4. concentrationconcentrated under reduced pressure
  5. customThe crude was purified by silica gel flash column chromatography (0-5% 7N NH3-MeOH in dichloromethane)

Quellen und Nachweise

ORD-Eintrag
ord-390cb25509ef4a378e6ae07799dc1be0
Quelldatensatz
uspto-grants-2014_10
Patentnummer
US08865726B2

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