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Ethyl chloroformate → HCID 135771836, Verbindung

HRID 1693027
Notizen
Druckvorschau

Reaktionsgleichung

Reaktionsgleichung von HRID 1693027
C(N(C(C)C)CC)(C)C.[NH2:10][C@@H:11]1[CH2:15][CH2:14][N:13]([C:16]2[C:25]3[C:20](=[CH:21][C:22]([CH3:26])=[CH:23][CH:24]=3)[N:19]=[C:18]([C:27]3[C:32]([F:33])=[CH:31][CH:30]=[CH:29][C:28]=3[OH:34])[N:17]=2)[CH2:12]1.Cl[C:36]([O:38][CH2:39][CH3:40])=[O:37].ClC([O-])=O>C1COCC1>[F:33][C:32]1[CH:31]=[CH:30][CH:29]=[C:28]([OH:34])[C:27]=1[C:18]1[N:17]=[C:16]([N:13]2[CH2:14][CH2:15][C@@H:11]([NH:10][C:36](=[O:37])[O:38][CH2:39][CH3:40])[CH2:12]2)[C:25]2[C:20](=[CH:21][C:22]([CH3:26])=[CH:23][CH:24]=2)[N:19]=1
KomponentenReaktionsbedingungenVersuchsvorschriftAufarbeitungQuellen und NachweiseNotizen zur Reaktion

Komponenten

6

Edukt 4

HCID 10928Ethyl chloroformateHCID 81531DiisopropylethylamineHCID 21226386CarbonochloridateHCID 136121403HCID 136121403, Verbindung

Produkt 1

HCID 135771836HCID 135771836, VerbindungAusbeute 93,2 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028
Tetrahydrofuran
Lösungsmittel

Reaktionsbedingungen

Temperatur
-40 °C

Versuchsvorschrift

At RT, diisopropyl ethylamine (130 μL, 0.74 mmol) was added to a solution of (R)-2-(4-(3-aminopyrrolidin-1-yl)-7-methylquinazolin-2-yl)-3-fluorophenol (125 mg, 0.37 mmol) in THF (10 mL), and the reaction was cooled to −40° C. Ethyl chloroformate (33 μL in 0.33 mL THF, 0.34 mmol) was added dropwise over a period of 10 minutes. After addition of the chloroformate was complete, the reaction mixture was warmed to RT, quenched with H2O, and extracted with CH2Cl2. The organic phase was dried over MgSO4, filtered, and concentrated. The residue was purified via silica gel chromatography using 0-10% EtOAc in a 1:1 mixture of hexanes and CH2Cl2 to give (R)-ethyl 1-(2-(2-fluoro-6-hydroxyphenyl)-7-methylquinazolin-4-yl)pyrrolidin-3-ylcarbamate (compound 10) (130 mg, 85%). 1H NMR (400 MHz, DMSO-d6) δ 8.19 (d, J=8.6 Hz, 1H), 7.58-7.57 (m, 2H), 7.38-7.29 (m, 2H), 6.76 (d, J=8.3 Hz, 1H), 6.72-6.67 (m, 1H), 4.25-4.21 (m, 1H), 4.16-4.13 (m, 2H), 4.07-3.97 (m, 3H), 3.84-3.82 (m, 1H), 2.52 (s, 3H), 2.24-2.16 (m, 1H), 2.04-2.00 (m, 1H), 1.16 (t, J=7.1 Hz, 3H) ppm. LC/MS: m/z 411.3 (M+H)+ at 2.24 min (10%-99% CH3CN (0.035% TFA)/H2O (0.05% TFA)).

Aufarbeitung

  1. temperaturethe reaction mixture was warmed to RT
  2. customquenched with H2O
  3. extractionextracted with CH2Cl2
  4. dry with materialThe organic phase was dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified via silica gel chromatography
  8. additionin a 1:1 mixture of hexanes and CH2Cl2

Quellen und Nachweise

ORD-Eintrag
ord-d34d9d4baffd4335ace9d8d03374764e
Quelldatensatz
uspto-grants-2012_04
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US08158637B2

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