Triethylamine → (R)-1-(4-(6-fluoro-2-(2-hydroxyphenyl)quinazolin-4-yl)piperazin-1-yl)-2-hydroxy-4,4-dimethylpentan-1-one

HRID 2062165Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2062165
[F:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[C:7]([C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=1[OH:18])[N:6]=[C:5]2[N:19]1[CH2:24][CH2:23][NH:22][CH2:21][CH2:20]1.C(N(CC)CC)C.[OH:32][C@H:33]([CH2:37][C:38]([CH3:41])([CH3:40])[CH3:39])[C:34](O)=[O:35].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>C(Cl)Cl>[F:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[C:7]([C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=1[OH:18])[N:6]=[C:5]2[N:19]1[CH2:20][CH2:21][N:22]([C:34](=[O:35])[C@H:33]([OH:32])[CH2:37][C:38]([CH3:41])([CH3:40])[CH3:39])[CH2:23][CH2:24]1

Komponenten

6

Edukt 4

HCID 8471TriethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 9898860(R)-2-hydroxy-4,4-dimethylpentanoic acidHCID 136121527HCID 136121527, Verbindung

Produkt 1

HCID 136121496(R)-1-(4-(6-fluoro-2-(2-hydroxyphenyl)quinazolin-4-yl)piperazin-1-yl)-2-hydroxy-4,4-dimethylpentan-1-oneAusbeute 86,9 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel2×

Versuchsvorschrift

To a solution of 2-(6-fluoro-4-(piperazin-1-yl)quinazolin-2-yl)phenol (200 mg, 0.61 mmol) in CH2Cl2 (5 mL) was added triethylamine (170 μL, 1.22 mmol) followed by the addition of (R)-2-hydroxy-4,4-dimethylpentanoic acid (116 mg, 0.79 mmol), then HATU (301 mg, 0.79 mmol). An additional 3 mL of CH2Cl2 were added, and the reaction was stirred for 3 h. After quenching with water, the mixture was extracted twice with CH2Cl2. The organic phase was dried over MgSO4 and concentrated. Purification via silica gel chromatography using 0-10% EtOAc in 50:50 CH2Cl2:hexanes yielded (R)-1-(4-(6-fluoro-2-(2-hydroxyphenyl)quinazolin-4-yl)piperazin-1-yl)-2-hydroxy-4,4-dimethylpentan-1-one (240 mg, 86%). m/z: M+1 obs=453.5; tR=3.19 minutes 1H NMR (400 MHz, DMSO-d6) δ 8.46 (m, 1H), 8.01 (m, 1H), 7.84 (m, 2H), 7.40 (m, 1H), 6.96 (m, 2H), 4.89 (d, J=7.1 Hz, 1H), 4.45 (m, 1H), 3.97 (m, 4H), 3.76 (m, 4H), 1.56 (m, 1H), 1.42 (m, 1H), 0.97 (s, 9H).

Aufarbeitung

  1. customAfter quenching with water
  2. extractionthe mixture was extracted twice with CH2Cl2
  3. dry with materialThe organic phase was dried over MgSO4
  4. concentrationconcentrated
  5. customPurification via silica gel chromatography

Quellen und Nachweise

ORD-Eintrag
ord-b33fd9af2e314a29b1b2dc4295683ef4
Quelldatensatz
uspto-grants-2012_10
Patentnummer
US08283354B2

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