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

HRID 2062280

Reaktionsgleichung

Reaktionsgleichung von HRID 2062280
[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.C(N(CC)CC)C.Cl[C:35]([O:37][C@H:38]1[CH2:42][CH2:41][O:40][CH2:39]1)=[O:36]>CN(C=O)C>[O:40]1[CH2:41][CH2:42][C@H:38]([O:37][C:35](=[O:36])[NH:1][CH2:2][C@H:3]2[CH2:8][CH2:7][CH2:6][N:5]([C:9]3[C:18]4[C:13](=[CH:14][C:15]([CH3:19])=[CH:16][CH:17]=4)[N:12]=[C:11]([C:20]4[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=4[OH:26])[N:10]=3)[CH2:4]2)[CH2:39]1

Komponenten

5

Edukt 3

HCID 8471TriethylamineHCID 22876378(3S)-oxolan-3-yl carbonochloridateHCID 136121476HCID 136121476, Verbindung

Produkt 1

HCID 136121578(S)-tetrahydrofuran-3-yl ((R)-1-(2-(2-hydroxyphenyl)-7-methylquinazolin-4-yl)piperidin-3-yl)methylcarbamate

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

To a stirred solution of 2-(4-((R)-3-(aminomethyl)piperidin-1-yl)-7-methylquinazolin-2-yl)phenol (200 mg, 0.57 mmol) in DMF under an N2 atmosphere at 0° C. was added triethylamine (115 mg, 1.14 mmol) followed by the dropwise addition of (S)-tetrahydrofuran-3-yl chloroformate (86 mg, 0.57 mmol). The reaction was allowed to warm to room temperature and was stirred for 2 h. The mixture was partitioned between H2O and CH2Cl2 and separated, and the aqueous layer was extracted twice with CH2Cl2. The organic layers were combined, dried over Na2SO4, filtered, and concentrated. Purification via silica gel chromatography using 4:1 CH2Cl2:EtOAc afforded (S)-tetrahydrofuran-3-yl((R)-1-(2-(2-hydroxyphenyl)-7-methylquinazolin-4-yl)piperidin-3-yl)methylcarbamate. LC/MS: m/z 463.5 (M+H)+ at 2.34 min (10%-99% CH3CN (0.035% TFA)/H2O (0.05% TFA)).

Aufarbeitung

  1. customThe mixture was partitioned between H2O and CH2Cl2
  2. customseparated
  3. extractionthe aqueous layer was extracted twice with CH2Cl2
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customPurification via silica gel chromatography

Quellen und Nachweise

ORD-Eintrag
ord-166a887787c3457d98b2b2652b27ff03
Quelldatensatz
uspto-grants-2012_10
Patentnummer
US08283354B2

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