1-Hydroxybenzotriazole → N-biphenyl-4-yl-3-[4-(2-bromo-5-fluoro-benzoyl)-piperazin-1-yl]-3-oxo-propionamide

HRID 1665600ノート

反応式

HRID 1665600 の反応式
C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C.[Br:20][C:21]1[CH:29]=[CH:28][C:27]([F:30])=[CH:26][C:22]=1[C:23]([OH:25])=O.CCN=C=NCCCN(C)C.Cl.Cl.[C:44]1([C:62]2[CH:67]=[CH:66][CH:65]=[CH:64][CH:63]=2)[CH:49]=[CH:48][C:47]([NH:50][C:51](=[O:61])[CH2:52][C:53](=[O:60])[N:54]2[CH2:59][CH2:58][NH:57][CH2:56][CH2:55]2)=[CH:46][CH:45]=1>CN(C=O)C.O>[C:44]1([C:62]2[CH:67]=[CH:66][CH:65]=[CH:64][CH:63]=2)[CH:45]=[CH:46][C:47]([NH:50][C:51](=[O:61])[CH2:52][C:53]([N:54]2[CH2:55][CH2:56][N:57]([C:23](=[O:25])[C:22]3[CH:26]=[C:27]([F:30])[CH:28]=[CH:29][C:21]=3[Br:20])[CH2:58][CH2:59]2)=[O:60])=[CH:48][CH:49]=1

参加物

8

反応物 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27781812-Bromo-5-fluorobenzoic acidHCID 66625265N-Biphenyl-4-yl-3-oxo-3-piperazin-1-yl-propionamide hydrochloride

生成物 1

HCID 44230949N-biphenyl-4-yl-3-[4-(2-bromo-5-fluoro-benzoyl)-piperazin-1-yl]-3-oxo-propionamide収率 38.1%

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 6228Dimethylformamide溶媒

反応条件

温度
10 °C

実験手順

HOBt (34 mg, 0.25 mmol) and DIPEA (67.9 mg, 0.51 mmol) were added to a stirred solution of 2-bromo-5-fluorobenzoic acid (46 mg, 0.21 mmol) in DMF (2 mL). The reaction mixture was cooled to 10° C. and EDCI.HCl (48 mg, 0.25 mmol) followed by N-biphenyl-4-yl-3-oxo-3-piperazin-1-yl-propionamide hydrochloride (75 mg, 0.2 mmol) were added. The reaction mixture was stirred at room temperature overnight, then diluted with water. The resulting precipitate was filtered, then purified by column chromatography using silica gel 60-120 mesh (80% ethyl acetate in hexane) to afford 40 mg (37%) of N-biphenyl-4-yl-3-[4-(2-bromo-5-fluoro-benzoyl)-piperazin-1-yl]-3-oxo-propionamide. LCMS: 524.09 (M+1)+, 96%. 1H NMR: (CDCl3): δ 9.6 (d, 1H), 7.6 (m, 7H), 7.42 (t, 2H), 7.34 (t, 1H), 7.0 (m, 2H), 3.96 (m, 2H), 3.7 (m, 4H), 3.5 (d, 2H), 3.3 (m, 2H).

後処理

  1. additionwere added
  2. filtrationThe resulting precipitate was filtered
  3. custompurified by column chromatography

出典と根拠

ORDレコード
ord-08b3c15d381041fcbb8f6e7fbb205e25
出典データセット
uspto-grants-2011_10
特許番号
US08039463B2

反応ノート

読み込み中…