Triethylamine → 6-chloro-4-cyclopropyl-4-(4-bromophenyl)-3-(2,2,2-trifluoroethyl)-3,4-dihydroquinazolin-2(1H)-one

HRID 19697Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 19697
[Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[NH:8][C:7](=[O:12])[N:6]([CH2:13][C:14]([F:17])([F:16])[F:15])[C:5]2([C:19]1[CH:24]=[CH:23][C:22]([Br:25])=[CH:21][CH:20]=1)O.C(N(CC)CC)C.S(Cl)(Cl)=O.[CH:37]1([Mg]Br)[CH2:39][CH2:38]1>C1COCC1>[Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[NH:8][C:7](=[O:12])[N:6]([CH2:13][C:14]([F:17])([F:16])[F:15])[C:5]2([CH:37]1[CH2:39][CH2:38]1)[C:19]1[CH:24]=[CH:23][C:22]([Br:25])=[CH:21][CH:20]=1

Komponenten

6

Edukt 4

HCID 8471TriethylamineHCID 24386Thionyl ChlorideHCID 593465966-chloro-4-(4-bromophenyl)-4-hydroxy-3-(2,2,2-trifluoroethyl)-3,4-dihydroquinazolin-2(1H)-oneHCID 178418630HCID 178418630, Verbindung

Produkt 1

HCID 118540706-chloro-4-cyclopropyl-4-(4-bromophenyl)-3-(2,2,2-trifluoroethyl)-3,4-dihydroquinazolin-2(1H)-one

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel2×

Versuchsvorschrift

To a −18° C. solution of 6-chloro-4-(4-bromophenyl)-4-hydroxy-3-(2,2,2-trifluoroethyl)-3,4-dihydroquinazolin-2(1H)-one (2 g, 4.6 mmol) in anhydrous THF (20 mL) was added triethylamine (2.6 mL, 18 mmol). The reaction was stirred for 5 min and then thionyl chloride (0.0.37 mL, 5 mmol) was added dropwise. After 10 min, 0.5M cyclopropylmagnesium bromide in THF (36 mL, 18 mmol) was added. The reaction mixture was warmed from −18° C. to 0° C. and allowed to stir for 6 hours and then quenched with 25 mL 1N aqueous HCl and extracted with 150 mL ethyl acetate. The organic layer was washed with brine (100 mL), dried over MgSO4, filtered, and concentrated in vacuo. Purification by normal phase chromatography (120 g silica gel cartridge, linear gradient 10-70% EtOAc/hexanes) followed by crystallization from hexanes gave 6-chloro-4-cyclopropyl-4-(4-bromophenyl)-3-(2,2,2-trifluoroethyl)-3,4-dihydroquinazolin-2(1H)-one as a green solid. 1H NMR (CDCl3, 400 MHz) δ 7.56 (s, NH); 7.46 (br d, 2H, J=8.61 Hz); 7.21 (dd, 1H, J=8.42 and 2.20 Hz); 7.12 (br d, 2H, J=7.14 Hz); 6.85 (br m, 1H); 6.68 (d, 1H, J=8.24 Hz); 4.27 (m, 2H); 1.6 (obs, 1H); 0.77 (m, 2H); 0.19 (m, 1H); 0.09 (m, 1H); MS (Electrospray): m/z 459.0 (M+H, Br=79).

Aufarbeitung

  1. waitAfter 10 min
  2. temperatureThe reaction mixture was warmed from −18° C. to 0° C.
  3. stirringto stir for 6 hours
  4. customquenched with 25 mL 1N aqueous HCl
  5. extractionextracted with 150 mL ethyl acetate
  6. washThe organic layer was washed with brine (100 mL)
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customPurification by normal phase chromatography (120 g silica gel cartridge, linear gradient 10-70% EtOAc/hexanes)
  11. customfollowed by crystallization from hexanes

Quellen und Nachweise

ORD-Eintrag
ord-81cccff6b87a473b89432072b88a8825
Quelldatensatz
uspto-grants-2010_06
Patentnummer
US07745452B2

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