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Potassium Carbonate → HCID 66838545, Verbindung

HRID 2102433
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Druckvorschau

Reaktionsgleichung

Reaktionsgleichung von HRID 2102433
FC(F)(F)C(O)=O.[Cl:8][C:9]1[C:10]([F:30])=[C:11]([NH:16][C:17]2[C:26]3[C:21](=[CH:22][C:23]([OH:29])=[C:24]([O:27][CH3:28])[CH:25]=3)[N:20]=[CH:19][N:18]=2)[CH:12]=[CH:13][C:14]=1[Cl:15].C(=O)([O-])[O-].[K+].[K+].CS(O[CH2:42][C@H:43]1[O:48][CH2:47][C@@H:46]2[CH2:49][CH2:50][CH2:51][N:45]2[CH2:44]1)(=O)=O>CN(C)C=O>[ClH:8].[Cl:8][C:9]1[C:10]([F:30])=[C:11]([NH:16][C:17]2[C:26]3[C:21](=[CH:22][C:23]([O:29][CH2:42][C@H:43]4[O:48][CH2:47][C@@H:46]5[CH2:49][CH2:50][CH2:51][N:45]5[CH2:44]4)=[C:24]([O:27][CH3:28])[CH:25]=3)[N:20]=[CH:19][N:18]=2)[CH:12]=[CH:13][C:14]=1[Cl:15]
KomponentenReaktionsbedingungenVersuchsvorschriftAufarbeitungQuellen und NachweiseNotizen zur Reaktion

Komponenten

5

Edukt 3

HCID 11430Potassium CarbonateHCID 86604086HCID 86604086, VerbindungHCID 136335142HCID 136335142, Verbindung

Produkt 1

HCID 66838545HCID 66838545, VerbindungAusbeute 38,2 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Reaktionsbedingungen

Temperatur
70 °C

Versuchsvorschrift

4-[(3,4-Dichloro-2-fluorophenyl)amino]-6-(methyloxy)quinazolin-7-ol trifluoroacetic acid salt (307 mg, 0.655 mmol) was dissolved in dimethylformamide (1 mL) and potassium carbonate (452 mg, 3.28 mmol) was added followed by (3S,8aS)-hexahydro-1H-pyrrolo[2,1-c][1,4]oxazin-3-ylmethyl methanesulfonate (250 mg, 1.06 mmol). The mixture was stirred at 70° C. for 41 h and then was partitioned between ethyl acetate and water. The aqueous portion was extracted with ethyl acetate. The combined organic portion was dried over sodium sulfate, filtered and concentrated in vacuo to afford an orange oil which was purified by column chromatography (ethyl acetate-ethanol 1:1). The purified material was dissolved in methanol and treated with 4M solution of HCl in 1,4-dioxane (0.1 mL) and the mixture was concentrated in vacuo to afford N-(3,4-dichloro-2-fluorophenyl)-7-{[(3S,8aS)-hexahydro-1H-pyrrolo[2,1-c][1,4]oxazin-3-ylmethyl]oxy}-6-(methyloxy)quinazolin-4-amine hydrochloride as a pale yellow solid (66 mg, 0.125 mmol, 19% yield). 1H NMR (400 MHz, d6-DMSO): 11.9-11.5 (m, 2H), 8.83 (s, 1H), 8.39-8.35 (m, 1H), 7.69 (dd, 1H), 7.62 (dd, 1H), 7.43 (s, 1H), 4.48-4.24 (m, 4H), 4.04 (s, 3H), 3.97-3.85 (m, 1H), 3.78-2.96 (m, 5H), 2.17-1.90 (m, 3H), 1.72-1.58 (m, 1H); MS (EI) for C23H23N4O3FCl2: 493 (MH+).

Aufarbeitung

  1. customwas partitioned between ethyl acetate and water
  2. extractionThe aqueous portion was extracted with ethyl acetate
  3. dry with materialThe combined organic portion was dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customto afford an orange oil which
  7. customwas purified by column chromatography (ethyl acetate-ethanol 1:1)
  8. dissolutionThe purified material was dissolved in methanol
  9. additiontreated with 4M solution of HCl in 1,4-dioxane (0.1 mL)
  10. concentrationthe mixture was concentrated in vacuo

Quellen und Nachweise

ORD-Eintrag
ord-76d672d2be3e407eafe9961cebb60c76
Quelldatensatz
uspto-grants-2009_08
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US07576074B2

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