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 394101ノート

反応式

HRID 394101 の反応式
[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]

参加物

4

反応物 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

生成物 1

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

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

反応条件

温度
0 °C

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-cdd9b2db54a94b32b04acc12c99f3e2d
出典データセット
uspto-grants-2004_10
特許番号
US06809199B2

反応ノート

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