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

HRID 9622

Reaktionsgleichung

Reaktionsgleichung von HRID 9622
[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]3[C:21]([O:23]C)=[O:22])=[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-].[Na+]>C(O)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:3]=[CH:4][C:5]([C:8]4[CH:13]=[CH:12][C:11]([C:14]([C@@H:16]5[CH2:20][CH2:19][CH2:18][C@H:17]5[C:21]([OH:23])=[O:22])=[O:15])=[CH:10][CH:9]=4)=[CH:6][CH:7]=3)=[N:30][C:29]=2[CH:31]=1

Komponenten

7

Edukt 4

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

Produkt 1

HCID 11374616trans-2-({4'-[(5,6-difluoro-1H-benzimidazol-2-yl)amino]biphenyl-4-yl}carbonyl)cyclopentanecarboxylic acidAusbeute 98,6 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 2631-ButanolLösungsmittelHCID 8028TetrahydrofuranLösungsmittel

Reaktionsbedingungen

Temperatur
90 °C

Versuchsvorschrift

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).

Aufarbeitung

  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)

Quellen und Nachweise

ORD-Eintrag
ord-2221d47fa7cf42b4b8a49b4187fa1ea1
Quelldatensatz
uspto-grants-2006_08
Patentnummer
US07091228B2

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