Triethylamine → (S)-Tetrahydrofuran-3-yl((S)-1-(2-(2-hydroxyphenyl)-7-methylquinazolin-4-yl)piperidin-3-yl)methylcarbamate

HRID 2062273

Reaktionsgleichung

Reaktionsgleichung von HRID 2062273
[NH2:1][CH2:2][C@@H:3]1[CH2:8][CH2:7][CH2:6][N:5]([C:9]2[C:18]3[C:13](=[CH:14][C:15]([CH3:19])=[CH:16][CH:17]=3)[N:12]=[C:11]([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=3[OH:26])[N:10]=2)[CH2:4]1.Cl[C:28]([O:30][C@H:31]1[CH2:35][CH2:34][O:33][CH2:32]1)=[O:29].C(N(CC)CC)C>CN(C=O)C>[OH:26][C:21]1[CH:22]=[CH:23][CH:24]=[CH:25][C:20]=1[C:11]1[N:10]=[C:9]([N:5]2[CH2:6][CH2:7][CH2:8][C@@H:3]([CH2:2][NH:1][C:28](=[O:29])[O:30][C@H:31]3[CH2:35][CH2:34][O:33][CH2:32]3)[CH2:4]2)[C:18]2[C:13](=[CH:14][C:15]([CH3:19])=[CH:16][CH:17]=2)[N:12]=1

Komponenten

5

Edukt 3

HCID 8471TriethylamineHCID 22876378(3S)-oxolan-3-yl carbonochloridateHCID 1361213552-(4-((S)-3-(Aminomethyl)piperidin-1-yl)-7-methylquinazolin-2-yl)phenol

Produkt 1

HCID 136121431(S)-Tetrahydrofuran-3-yl((S)-1-(2-(2-hydroxyphenyl)-7-methylquinazolin-4-yl)piperidin-3-yl)methylcarbamate

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel2×

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

2-(4-((S)-3-(Aminomethyl)piperidin-1-yl)-7-methylquinazolin-2-yl)phenol (126.8 mg, 0.364 mmol) was dissolved in 5 mL anhydrous DMF and cooled to 0° C., and a solution of (S)-tetrahydrofuran-3-yl chloroformate (65.4 mg, 0.436 mmol) in 200 □1 of DMF was added dropwise followed by the addition of triethylamine (74 mg, 0.102 mL, 0.728 mmol). The reaction was allowed to warm to room temperature and was complete after two hours. The mixture was partitioned between H2O and CH2Cl2, separated, and the aqueous layer was extracted twice with CH2Cl2. The combined organic phases were dried over Na2SO4, filtered, and concentrated to a yellow solid. Purification via silica gel chromatography using 98% CH2Cl2/2% MeOH gave (S)-tetrahydrofuran-3-yl ((S)-1-(2-(2-hydroxyphenyl)-7-methylquinazolin-4-yl)piperidin-3-yl)methylcarbamate as an off white solid (116 mg, 69%). LC/MS: m/z 463.5 (M+H)+ at 2.37 min (10%-99% CH3CN (0.035% TFA)/H2O (0.05% TFA)).

Aufarbeitung

  1. temperatureto warm to room temperature
  2. customThe mixture was partitioned between H2O and CH2Cl2
  3. customseparated
  4. extractionthe aqueous layer was extracted twice with CH2Cl2
  5. dry with materialThe combined organic phases were dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated to a yellow solid
  8. customPurification via silica gel chromatography

Quellen und Nachweise

ORD-Eintrag
ord-da6576fc3960463d870229710f91d2aa
Quelldatensatz
uspto-grants-2012_10
Patentnummer
US08283354B2

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