1-Butanol → trans-2-({4'-[(5,7-Difluoro-1,3-benzothiazol-2-yl)amino]-1,1'-biphenyl-4-yl}carbonyl)cyclopentanecarboxylic acid

HRID 30934

Reaktionsgleichung

Reaktionsgleichung von HRID 30934
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][C:11]([C:14]([C@@H:16]3[CH2:19][CH2:18][C@H:17]3[C:20]([O:22]C)=[O:21])=[O:15])=[CH:10][CH:9]=2)=[CH:4][CH:3]=1.Cl[C:25]1[S:26][C:27]2[C:33]([F:34])=[CH:32][C:31]([F:35])=[CH:30][C:28]=2[N:29]=1.Cl.[OH-].[Na+].[CH2:39](O)CCC>>[F:35][C:31]1[CH:32]=[C:33]([F:34])[C:27]2[S:26][C:25]([NH:1][C:2]3[CH:3]=[CH:4][C:5]([C:8]4[CH:9]=[CH:10][C:11]([C:14]([C@@H:16]5[CH2:39][CH2:19][CH2:18][C@H:17]5[C:20]([OH:22])=[O:21])=[O:15])=[CH:12][CH:13]=4)=[CH:6][CH:7]=3)=[N:29][C:28]=2[CH:30]=1

Komponenten

6

Edukt 5

HCID 2631-ButanolHCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 219857472-Chloro-5,7-difluorobenzo[D]thiazoleHCID 58681294Methyl trans-2-[(4'-amino-1,1'-biphenyl-4-yl)carbonyl]cyclobutanecarboxylate

Produkt 1

HCID 11719907trans-2-({4'-[(5,7-Difluoro-1,3-benzothiazol-2-yl)amino]-1,1'-biphenyl-4-yl}carbonyl)cyclopentanecarboxylic acidAusbeute 58 %

Reaktionsbedingungen

Temperatur
90 °C

Versuchsvorschrift

To a solution of methyl trans-2-[(4′-amino-1,1′-biphenyl-4-yl)carbonyl]cyclobutanecarboxylate (80 mg, 0.25 mmol) in n-butanol (8 mL) was added 2-chloro-5,7-difluoro-1,3-benzothiazole (102 mg, 0.49 mmol) and HCl (4.0 M in dioxane, 0.2 mL). The resulting reaction mixture was heated at 90° C. overnight. The mixture was evaporated to dryness, and the residue was brought up in MeOH. Then 1 N aqueous NaOH (2.0 mL, 2.0 mmol) was added, and the reaction mixture was stirred at 50° C. overnight. The reaction mixture was concentrated and the residue was suspended in water. Conc. HCl was added to adjust the acidity to pH 1, and the suspension was extracted with EtOAc. The combined organic phases were washed with brine, dried over sodium sulfate, filtered, and concentrated. The residue was brought up in MeOH, and the precipitate was collected by filtration and dried under vacuum oven to afford trans-2-({4′-[(5,7-difluoro-1,3-benzothiazol-2-yl)amino]-1,1′-biphenyl-4-yl}carbonyl)cyclopentanecarboxylic acid (65 mg, 58%). LC-MS ret. time 3.75; m/z 479.2 (MH+). 1H NMR (400 MHz, DMSO-d6) δ 1.55-1.84 (m, 4H), 2.01 (m, 1H), 2.18 (m, 1H), 3.22 (q, 1H), 4.09 (q, 1H), 7.15 (m, 1H), 7.40 (m, 1H), 7.83 (m, 4H), 7.87 (d, 2H), 8.05 (d, 2H), 11.00 (s, 1H), 12.12 (s, 1H).

Aufarbeitung

  1. customThe resulting reaction mixture
  2. customThe mixture was evaporated to dryness
  3. concentrationThe reaction mixture was concentrated
  4. additionConc. HCl was added
  5. extractionthe suspension was extracted with EtOAc
  6. washThe combined organic phases were washed with brine
  7. dry with materialdried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated
  10. filtrationthe precipitate was collected by filtration
  11. customdried under vacuum oven

Quellen und Nachweise

ORD-Eintrag
ord-3284431c08c04504b2c5bdfd4d4ee9f3
Quelldatensatz
uspto-grants-2008_09
Patentnummer
US07423156B2

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