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 394098노트

반응식

HRID 394098 반응식
[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]

참가 물질

6

반응물 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

생성물 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

시약·촉매·용매 1

HCID 63651,1-Dichloroethane용매

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-7ca12ece37684cebaba1c0bccb197c4b
출처 데이터셋
uspto-grants-2004_10
특허 번호
US06809199B2

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