Reaktion #2149324

Reaktionsgleichung

HATU

2-(7-Methyl-4-(piperazin-1-yl)quinazolin-2-yl)phenol

(R)-2-hydroxy-4,4-dimethylpentanoic acid

HATU

triethylamine

→

(R)-2-hydroxy-1-(4-(2-(2-hydroxyphenyl)-7-methylquinazolin-4-yl)piperazin-1-yl)-4,4-dimethylpentan-1-one

Ausbeute 79.8%

Lösungsmittel

DMF

Reaktionsbedingungen

Aufarbeitung

1. 1
   Temperaturto warm to 10° C
2. 2
   Sonstigeit was quenched with an equal portion of ice water
3. 3
   SonstigeA yellow precipitate formed which
4. 4
   Filtrationwas collected by vacuum filtration
5. 5
   workup.DISSOLUTIONdissolved in CH2Cl2
6. 6
   Filtrationfiltered
7. 7
   Einengenconcentrated
8. 8
   Sonstigeto give a viscous yellow-orange oil
9. 9
   SonstigeThe crude material was purified via silica gel chromatography

Vorschrift

2-(7-Methyl-4-(piperazin-1-yl)quinazolin-2-yl)phenol (250 mg, 0.74 mmol) was suspended in anhydrous DMF (5 mL) and cooled to 0° C. internal temperature. Under an N2 atmosphere, (R)-2-hydroxy-4,4-dimethylpentanoic acid (125.4 mg, 0.858 mmol) was added followed by triethylamine (0.218 mL, 1.56 mmol). To this stirring solution was added HATU (356 mg, 0.936 mmol). After the complete addition of HATU, the mixture was allowed to warm to 10° C. After 45 min the reaction was complete, and it was quenched with an equal portion of ice water. A yellow precipitate formed which was collected by vacuum filtration and dissolved in CH2Cl2. This solution was desiccated with Na2SO4, filtered, and concentrated to give a viscous yellow-orange oil. The crude material was purified via silica gel chromatography using 88% CH2Cl2-hexanes (1:1) and 12% EtOAc to afford (R)-2-hydroxy-1-(4-(2-(2-hydroxyphenyl)-7-methylquinazolin-4-yl)piperazin-1-yl)-4,4-dimethylpentan-1-one as a faint yellow foam (265 mg, 76%). LC/MS: m/z 449.3 (M+H)+ at 2.75 min (10%-99% CH3CN (0.035% TFA)/H2O (0.05% TFA)). 1H NMR (400 MHz, DMSO-d6) δ 8.46 (dd, J=8.2, 1.8 Hz, 1H), 8.02 (d, J=8.5 Hz, 1H), 7.70 (s, 1H), 7.41-7.37 (m, 2H), 6.97-6.93 (m, 2H), 4.89 (d, J=7.2 Hz, 1H), 4.49-4.44 (m, 1H), 4.06-3.67 (m,8), 2.52 (s, 3H), 1.56 (dd, J=14.3, 3.0 Hz, 1H), 1.42 (dd, J=14.3, 8.8 Hz, 1H), 0.97 (s, 9H)

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