1-Hydroxybenzotriazole → 1-[4-(2-Bromo-benzoyl)-piperazine-1-carbonyl]-cyclopropanecarboxylic acid biphenyl-4-ylamide

HRID 1665681ノート

反応式

HRID 1665681 の反応式
[CH3:1][CH2:2]N(C(C)C)C(C)C.[C:10]1([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[CH:15]=[CH:14][C:13]([N:16](C)[C:17](=[O:22])[CH2:18][C:19]([OH:21])=O)=[CH:12][CH:11]=1.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl.Cl.[Br:53][C:54]1[CH:59]=[CH:58][CH:57]=[CH:56][C:55]=1[C:60]([N:62]1[CH2:67][CH2:66][NH:65][CH2:64][CH2:63]1)=[O:61]>CN(C=O)C.O>[C:10]1([C:24]2[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=2)[CH:11]=[CH:12][C:13]([NH:16][C:17]([C:18]2([C:19]([N:65]3[CH2:64][CH2:63][N:62]([C:60](=[O:61])[C:55]4[CH:56]=[CH:57][CH:58]=[CH:59][C:54]=4[Br:53])[CH2:67][CH2:66]3)=[O:21])[CH2:2][CH2:1]2)=[O:22])=[CH:14][CH:15]=1

参加物

8

反応物 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 57875814N-biphenyl-4-yl-N-methyl-malonamic acidHCID 66625832(2-Bromo-phenyl)-piperazin-1-yl-methanone hydrochloride

生成物 1

HCID 442315631-[4-(2-Bromo-benzoyl)-piperazine-1-carbonyl]-cyclopropanecarboxylic acid biphenyl-4-ylamide収率 12.95%

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 6228Dimethylformamide溶媒

実験手順

DIPEA (140 mg, 1.1 mmol) was added to a stirred solution of N-biphenyl-4-yl-N-methyl-malonamic acid (100 mg, 0.37 mmol) in DMF (2.0 mL) followed by HOBt (60 mg, 0.44 mmol) and EDCI.HCl (85 mg, 0.44 mmol). After 2 minutes of stirring, (2-bromo-phenyl)-piperazin-1-yl-methanone hydrochloride (136 mg, 0.44 mmol) was added and stirring was continued at ambient temperature overnight. The reaction mixture was diluted with water, extracted with ethyl acetate, washed with brine and concentrated under reduced pressure to get the residue. Purification by column chromatography, (using silica gel 60-120, 100% EtOAc as eluent) to afford 14.8 mg (12.95%) of 1-[4-(2-bromo-benzoyl)-piperazine-1-carbonyl]-cyclopropanecarboxylic acid biphenyl-4-ylamide. LC/MS [M+H]+: 520.12, 89.73%. 1H NMR (300 MHz, CDCl3): δ 7.7-7.3 (m, 2H), 7.3-7.2 (m, 2H), 4.0-3.6 (m, 5H), 3.58-3.4 (m, 5H), 3.4-3.2 (m, 3H).

後処理

  1. stirringstirring
  2. waitwas continued at ambient temperature overnight
  3. extractionextracted with ethyl acetate
  4. washwashed with brine
  5. concentrationconcentrated under reduced pressure
  6. customto get the residue
  7. customPurification by column chromatography, (using silica gel 60-120, 100% EtOAc as eluent)

出典と根拠

ORDレコード
ord-31990992e7c6486091f949140db51b0e
出典データセット
uspto-grants-2011_10
特許番号
US08039463B2

反応ノート

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