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

HRID 2079253Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2079253
[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 was 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) d 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) ppm.

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-32971121e1774c639287dba262f3fde4
Quelldatensatz
uspto-grants-2011_04
Patentnummer
US07928107B2

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