Acetic Acid → Tert-butyl 4-{[5-(2-chlorophenyl)-1-(2,6-dichlorophenyl)-2-oxo-1,2,3,4-tetrahydroquinazolin-7-yl]methyl}-3-methylpiperazine-1-carboxylate

HRID 394098ノート

反応式

HRID 394098 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]([CH:18]=O)[CH:15]=[C:14]2[C:9]=1[CH2:10][NH:11][C:12](=[O:28])[N:13]2[C:20]1[C:25]([Cl:26])=[CH:24][CH:23]=[CH:22][C:21]=1[Cl:27].[C:29]([N:36]1[CH2:41][CH2:40][NH:39][CH:38]([CH3:42])[CH2:37]1)([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(O)(=O)C>ClC(Cl)C>[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:39]2[CH2:40][CH2:41][N:36]([C:29]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30])[CH2:37][CH:38]2[CH3:42])[CH:15]=[C:14]2[C:9]=1[CH2:10][NH:11][C:12](=[O:28])[N:13]2[C:20]1[C:21]([Cl:27])=[CH:22][CH:23]=[CH:24][C:25]=1[Cl:26]

参加物

6

反応物 4

HCID 176Acetic AcidHCID 2756810tert-Butyl 3-methylpiperazine-1-carboxylateHCID 5049666Sodium triacetoxyborohydrideHCID 226481625-(2-Chlorophenyl)-1-(2,6-dichlorophenyl)-2-oxo-1,2,3,4-tetrahydroquinazoline-7-carbaldehyde

生成物 1

HCID 22648157Tert-butyl 4-{[5-(2-chlorophenyl)-1-(2,6-dichlorophenyl)-2-oxo-1,2,3,4-tetrahydroquinazolin-7-yl]methyl}-3-methylpiperazine-1-carboxylate

試薬・触媒・溶媒 1

HCID 63651,1-Dichloroethane溶媒

実験手順

A solution of 5-(2-chlorophenyl)-1-(2,6-dichlorophenyl)-2-oxo-1,2,3,4-tetrahydroquinazoline-7-carbaldehyde (Intermediate AAA1, 208 mg, 0.48 mmol) and 1-BOC-3-methylpiperazine (96 mg, 0.48 mmol) in dichloroethane (5 mL) was stirred at rt for 30 min. To this was added sodium triacetoxyborohydride (150 mg, 0.67 mmol) followed by acetic acid (29 mg, 0.48 mmol). The resulting reaction mixture was stirred at rt for 20 h. The reaction was quenched with 2N NaOH solution (6 mL) followed by extraction with ethyl acetate (100 mL×2). The organic layer was washed with brine and dried over anhydrous sodium sulfate. Removal of the solvent and subsequent purification by flash chromatography using 25% acetone/hexane provided tert-butyl 4-{[5-(2-chlorophenyl)-1-(2,6-dichlorophenyl)-2-oxo-1,2,3,4-tetrahydroquinazolin-7-yl]methyl}-3-methylpiperazine-1-carboxylate as a white solid. 1H NMR (CDCl3, 500 MHz): δ 0.98 (s, 3H), 1.46 (s, 9H), 2.06 (brs, 1H), 2.39 (brs, 1H), 2.60 (brs, 1H), 2.82 (brs, 1H), 3.05 (brs, 1H), 3.15 (m, 1H), 3.54 (brs, 2H), 3.82 (brs, 1H), 4.34 (abq, 2H, J=14.2 Hz), 5.15 (s, 1H), 6.16 (d, 1H, J=5.2 Hz), 6.88 (s, 1H), 7.20-7.60 (m, 7H). MS (API-ES+): 617 (M+H).

後処理

  1. customThe resulting reaction mixture
  2. customThe reaction was quenched with 2N NaOH solution (6 mL)
  3. extractionfollowed by extraction with ethyl acetate (100 mL×2)
  4. washThe organic layer was washed with brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. customRemoval of the solvent and subsequent purification by flash chromatography

出典と根拠

ORDレコード
ord-7ca12ece37684cebaba1c0bccb197c4b
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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