Acetic Acid Mixture with Hydrobromic Acid → 5-(2-chlorophenyl)-1-(2,6-dichlorophenyl)-7-[(3-methylpiperazin-1-yl)methyl]-3,4-dihydroquinazolin-2(1H)-one

HRID 394101Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 394101
[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[CH:17]=[C:16]([CH2:18][N:19]2[CH2:24][CH2:23][N:22](C(OCC3C=CC=CC=3)=O)[CH:21]([CH3:35])[CH2:20]2)[CH:15]=[C:14]2[C:9]=1[CH2:10][NH:11][C:12](=[O:44])[N:13]2[C:36]1[C:41]([Cl:42])=[CH:40][CH:39]=[CH:38][C:37]=1[Cl:43].Br.CC(O)=O>C(Cl)Cl>[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[CH:17]=[C:16]([CH2:18][N:19]2[CH2:24][CH2:23][NH:22][CH:21]([CH3:35])[CH2:20]2)[CH:15]=[C:14]2[C:9]=1[CH2:10][NH:11][C:12](=[O:44])[N:13]2[C:36]1[C:37]([Cl:43])=[CH:38][CH:39]=[CH:40][C:41]=1[Cl:42]

Komponenten

4

Edukt 2

HCID 21893785Acetic Acid Mixture with Hydrobromic AcidHCID 22647930Benzyl 4-{[5-(2-chlorophenyl)-1-(2,6-dichlorophenyl)-2-oxo-1,2,3,4-tetrahydroquinazolin-7-yl]methyl}-2-methylpiperazine-1-carboxylate

Produkt 1

HCID 101861125-(2-chlorophenyl)-1-(2,6-dichlorophenyl)-7-[(3-methylpiperazin-1-yl)methyl]-3,4-dihydroquinazolin-2(1H)-one

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

To a solution of benzyl 4-{[5-(2-chlorophenyl)-1-(2,6-dichlorophenyl)-2-oxo-1,2,3,4-tetrahydroquinazolin-7-yl]methyl}-2-methylpiperazine-1-carboxylate (105 mg, 0.16 mmol) in methylene chloride (2 mL) at 0° C. was added 30% HBr/HOAc (0.32 mL, 1.62 mmol) slowly. The resulting reaction mixture was stirred at 0° C. for 30 min, and then at rt for 30 min. The reaction was quenched with water, then added 5N NaOH solution to pH ˜1, and extracted with methylene chloride (50 mL×3) and ethyl acetate (50 mL×2). The organic layer was washed with brine and dried over anhydrous sodium sulfate. Removal of the solvent and subsequent purification by preparative thin layer chromatography using 8% of 2N ammonium in methanol/methylene chloride as eluent provided 5-(2-chlorophenyl)-1-(2,6-dichlorophenyl)-7-[(3-methylpiperazin-1-yl)methyl]-3,4-dihydroquinazolin-2(1H)-one as a white solid. 1H NMR (CDCl3, 500 MHz): δ 1.06 (d, 3H, J=4.8 Hz), 1.72 (m, 1H), 2.06 (m, 1H), 2.69 (m, 2H), 2.82 (t, 2H, J=9.3 Hz), 2.98 (d, 1H, J=11.9 Hz), 3.40 (m, 2H), 4.34 (abq, 2H, J=14.4 Hz), 5.10 (s, 1H), 6.17 (s, 1H), 6.84 (s, 1H), 7.30-7.60 (m, 7H). MS (API-ES+): 517 (M+H).

Aufarbeitung

  1. customThe resulting reaction mixture
  2. waitat rt for 30 min
  3. customThe reaction was quenched with water
  4. additionadded 5N NaOH solution to pH ˜1
  5. extractionextracted with methylene chloride (50 mL×3) and ethyl acetate (50 mL×2)
  6. washThe organic layer was washed with brine
  7. dry with materialdried over anhydrous sodium sulfate
  8. customRemoval of the solvent and subsequent purification by preparative thin layer chromatography

Quellen und Nachweise

ORD-Eintrag
ord-cdd9b2db54a94b32b04acc12c99f3e2d
Quelldatensatz
uspto-grants-2004_10
Patentnummer
US06809199B2

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