1-Butanol → ({4'-[(5,6-difluoro-1H-benzimidazol-2-yl)amino]biphenyl-4-yl}carbonyl)cyclopentanecarboxylic acid

HRID 2427404ノート

反応式

HRID 2427404 の反応式
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][C:11]([C:14]([CH:16]3[CH2:20][CH2:19][CH2:18][CH:17]3C(OC)=O)=[O:15])=[CH:10][CH:9]=2)=[CH:4][CH:3]=1.Cl[C:26]1[NH:30][C:29]2[CH:31]=[C:32]([F:36])[C:33]([F:35])=[CH:34][C:28]=2[N:27]=1.Cl.[OH-:38].[Na+].[CH2:40]([OH:44])CCC>O1CCCC1>[F:36][C:32]1[C:33]([F:35])=[CH:34][C:28]2[NH:27][C:26]([NH:1][C:2]3[CH:7]=[CH:6][C:5]([C:8]4[CH:9]=[CH:10][C:11]([C:14]([C:16]5([C:40]([OH:44])=[O:38])[CH2:17][CH2:18][CH2:19][CH2:20]5)=[O:15])=[CH:12][CH:13]=4)=[CH:4][CH:3]=3)=[N:30][C:29]=2[CH:31]=1

参加物

7

反応物 5

HCID 2631-ButanolHCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 4694162-chloro-5,6-difluoro-1H-benzimidazoleHCID 21985670Methyl 2-[(4'-aminobiphenyl-4-yl)carbonyl]cyclopentanecarboxylate

生成物 1

HCID 86634970({4'-[(5,6-difluoro-1H-benzimidazol-2-yl)amino]biphenyl-4-yl}carbonyl)cyclopentanecarboxylic acid収率 3%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

反応条件

温度
90 °C

実験手順

Methyl 2-[(4′-aminobiphenyl-4-yl)carbonyl]cyclopentanecarboxylate (264 mg, 0.02 mmol) was dissolved in n-butanol (8 mL), 2-chloro-5,6-difluoro-1H-benzimidazole (185 mg, 0.98 mmol) and 4 N HCl (0.2 mL) were then added, and the resulting mixture was heated at 90° C. for 5 h. The mixture was then cooled to rt, and solvent was removed under reduced pressure. The residue was dissolved in methanol (5 mL) and tetrahydrofuran (5 mL), and then treated with 1 N aqueous sodium hydroxide (2.45 mL, 2.45 mmol). The mixture was stirred at rt for 16 h and then concentrated under reduced pressure. The residue was purified by preparative reverse-phase HPLC (water/acetonitrile gradient, containing 0.1% TFA) to afford trans-2-[({4′-[(5,6-difluoro-1H-benzimidazol-2-yl)amino]biphenyl-4-yl}carbonyl)cyclopentanecarboxylic acid (9.1 mg, 3%). LC-MS m/z 462.3 (MH+), ret. time 3.23 min; 1H NMR (300 MHz, DMSO-d6) δ 1.69-1.81 (m, 4H), 1.98-2.18 (m, 2H), 3.14-3.22 (m, 1H), 4.04-4.09 (m, 1H), 7.38 (t, 2H), 7.77-7.84 (m, 6H), 8.05 (d, 2H).

後処理

  1. temperatureThe mixture was then cooled to rt
  2. customsolvent was removed under reduced pressure
  3. dissolutionThe residue was dissolved in methanol (5 mL)
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was purified by preparative reverse-phase HPLC (water/acetonitrile gradient, containing 0.1% TFA)

出典と根拠

ORDレコード
ord-9ae83242e8494763a880ecc8a702d4b3
出典データセット
uspto-grants-2011_06
特許番号
US07968576B2

反応ノート

読み込み中…