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

HRID 539007Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 539007
[OH:1][CH2:2][CH2:3][NH:4][C:5]([NH:7][NH:8][C:9](=O)[C:10]1[CH:15]=[CH:14][C:13]([C:16]2[CH:17]=[N:18][N:19]3[CH:24]=[CH:23][C:22]([N:25]4[C@@H:29]([CH:30]([CH3:32])[CH3:31])[CH2:28][O:27][C:26]4=[O:33])=[N:21][C:20]=23)=[CH:12][CH:11]=1)=[O:6].C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C(N(CC)CC)C.C(Cl)(Cl)(Cl)Cl>ClCCl.CC#N.CCOC(C)=O>[OH:1][CH2:2][CH2:3][NH:4][C:5]1[O:6][C:9]([C:10]2[CH:11]=[CH:12][C:13]([C:16]3[CH:17]=[N:18][N:19]4[CH:24]=[CH:23][C:22]([N:25]5[C@@H:29]([CH:30]([CH3:32])[CH3:31])[CH2:28][O:27][C:26]5=[O:33])=[N:21][C:20]=34)=[CH:14][CH:15]=2)=[N:8][N:7]=1

Komponenten

8

Edukt 4

HCID 5943Carbon TetrachlorideHCID 8471TriethylamineHCID 11776TriphenylphosphineHCID 67033962(S)-N-(2-hydroxyethyl)-2-(4-(5-(4-isopropyl-2-oxooxazolidin-3-yl)pyrazolo[1,5-a]pyrimidin-3-yl)benzoyl)hydrazinecarboxamide

Produkt 1

HCID 68088822(S)-3-(3-(4-(5-(2-hydroxyethylamino)-1,3,4-oxadiazol-2-yl)phenyl)pyrazolo[1,5-a]pyrimidin-5-yl)-4-isopropyloxazolidin-2-oneAusbeute 35,9 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 6342AcetonitrileLösungsmittelHCID 6344DichloromethaneLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Reaktionsbedingungen

Temperatur
50 °C

Versuchsvorschrift

To a suspension of (S)—N-(2-hydroxyethyl)-2-(4-(5-(4-isopropyl-2-oxooxazolidin-3-yl)pyrazolo[1,5-a]pyrimidin-3-yl)benzoyl)hydrazinecarboxamide (14.4 mg, 0.031 mmol) in dichloromethane (1 mL) and MeCN (1 mL) was added PS-triphenylphosphine resin (0.054 g, 2.28 mmol/g, 0.123 mmol), triethylamine (44 μL, 0.308 mmol), and CCl4 (12 μL, 0.123 mmol), and the reaction mixture was heated to 50° C. for 4 hours. After the mixture was cooled at ambient temperature, the reaction mixture was treated with EtOAc, washed with water, dried over MgSO4, and concentrated under reduced pressure. The crude was then purified by preparative plate silica gel chromatography (10% MeOH in dichloromethane) to afford 5 mg (35%) of (S)-3-(3-(4-(5-(2-hydroxyethylamino)-1,3,4-oxadiazol-2-yl)phenyl)pyrazolo[1,5-a]pyrimidin-5-yl)-4-isopropyloxazolidin-2-one. 1H NMR (400 MHz, CDCl3) δ 8.60 (d, 1H), 8.43 (s, 1H), 8.08 (m, 3H), 7.92 (d, 2H), 4.96 (m, 1H), 4.44 (m, 2H), 3.94 (t, 2H), 3.65 (m, 2H), 2.88 (m, 1H), 1.09 (d, 3H), 0.95 (d, 3H); LCMS (APCI+) m/z 450.6 [M+H]+.

Aufarbeitung

  1. temperatureAfter the mixture was cooled at ambient temperature
  2. washwashed with water
  3. dry with materialdried over MgSO4
  4. concentrationconcentrated under reduced pressure
  5. customThe crude was then purified by preparative plate silica gel chromatography (10% MeOH in dichloromethane)

Quellen und Nachweise

ORD-Eintrag
ord-e50f7a0467164d5bb4fb69c7ad7c2e79
Quelldatensatz
uspto-grants-2014_10
Patentnummer
US08865726B2

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