Triethylamine → (R)-2-hydroxy-1-(4-(2-(2-hydroxyphenyl)quinazolin-4-yl)piperazin-1-yl)butan-1-one

HRID 2062178Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2062178
[N:1]1([C:7]2[C:16]3[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=3)[N:10]=[C:9]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=3[OH:23])[N:8]=2)[CH2:6][CH2:5][NH:4][CH2:3][CH2:2]1.C(N(CC)CC)C.[OH:31][C@H:32]([CH2:36][CH3:37])[C:33](O)=[O:34].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>C(Cl)Cl>[OH:31][C@H:32]([CH2:36][CH3:37])[C:33]([N:4]1[CH2:3][CH2:2][N:1]([C:7]2[C:16]3[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=3)[N:10]=[C:9]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=3[OH:23])[N:8]=2)[CH2:6][CH2:5]1)=[O:34]

Komponenten

6

Edukt 4

HCID 8471TriethylamineHCID 449265(R)-2-Hydroxybutyric acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 1361053622-(4-(Piperazin-1-yl)quinazolin-2-yl)phenol

Produkt 1

HCID 136121367(R)-2-hydroxy-1-(4-(2-(2-hydroxyphenyl)quinazolin-4-yl)piperazin-1-yl)butan-1-oneAusbeute 88 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

To a solution of 2-(4-(piperazin-1-yl)quinazolin-2-yl)phenol (250 mg, 0.82 mmol) in CH2Cl2 (6 mL) was added triethylamine (227 μL, 1.63 mmol) followed by the addition of (R)-2-hydroxybutanoic acid (110 mg, 1.06 mmol) and HATU (380 mg, 1.00 mmol). The reaction mixture was stirred at room temperature for 3 h and then quenched with H2O. The aqueous layer was extracted twice with CH2Cl2, dried over MgSO4, filtered, and concentrated. Purification via silica gel chromatography using 0-10% EtOAc in 50:50 CH2Cl2:hexanes gave (R)-2-hydroxy-1-(4-(2-(2-hydroxyphenyl)quinazolin-4-yl)piperazin-1-yl)butan-1-one (280 mg, 88%). LC/MS: m/z 393.3 (M+H)+ at 2.17 min (10%-99% CH3CN (0.035% TFA)/H2O (0.05% TFA)). 1H NMR (400 MHz, DMSO-d6) δ 8.47 (m, 1H), 8.12 (d, J=8.3 Hz, 1H), 7.89 (m, 2H), 7.57 (m, 1H), 7.40 (m, 1H), 6.96 (m, 2H), 4.92 (d, J=7.1 Hz, 1H), 3.88 (m, 8H), 1.67 (m, 1H), 1.51 (m, 1H), 0.91 (t, J=7.4 Hz, 3H).

Aufarbeitung

  1. customquenched with H2O
  2. extractionThe aqueous layer was extracted twice with CH2Cl2
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customPurification via silica gel chromatography

Quellen und Nachweise

ORD-Eintrag
ord-314d376122154c19964c7d08cd5f998b
Quelldatensatz
uspto-grants-2012_10
Patentnummer
US08283354B2

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