1-Butanol → Racemic trans-2-({4'-[(4,6-difluoro-1,3-benzothiazol-2-yl)amino]-1,1'-biphenyl-4-yl}-carbonyl)cyclopentanecarboxylic acid

HRID 9613

Reaktionsgleichung

Reaktionsgleichung von HRID 9613
[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[CH:33]=[C:32]([F:34])[CH:31]=[C:30]([F:35])[C:28]=2[N:29]=1.[OH-].[Na+].[CH2:38](O)CCC>>[F:35][C:30]1[C:28]2[N:29]=[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[CH2:38][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)[S:26][C:27]=2[CH:33]=[C:32]([F:34])[CH:31]=1

Komponenten

5

Edukt 4

HCID 2631-ButanolHCID 14798Sodium HydroxideHCID 20498832-Chloro-4,6-difluorobenzothiazoleHCID 58681294Methyl trans-2-[(4'-amino-1,1'-biphenyl-4-yl)carbonyl]cyclobutanecarboxylate

Produkt 1

HCID 44467044Racemic trans-2-({4'-[(4,6-difluoro-1,3-benzothiazol-2-yl)amino]-1,1'-biphenyl-4-yl}-carbonyl)cyclopentanecarboxylic acidAusbeute 43 %

Reaktionsbedingungen

Temperatur
90 °C

Versuchsvorschrift

To a solution of racemic methyl trans-2-[(4′-amino-1,1′-biphenyl-4-yl)carbonyl]cyclobutane-carboxylate (250 mg, 0.77 mmol) in n-butanol (15 mL) was added 2-chloro-4,6-difluoro-1,3-benzothiazole (318 mg, 1.55 mmol), and the resulting solution was heated at 90° C. overnight. The mixture was then evaporated to dryness under reduced pressure, and the residue was brought up in MeOH. Then 1 N aqueous NaOH (8.0 mL, 8.0 mmol) was added to the suspension, and the reaction mixture was stirred at 50° C. overnight. The reaction mixture was concentrated under reduced pressure, and the residue was suspended in water. Conc. HCl was added to adjust the acidity to pH 1, and the mixture 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, washed with MeOH, EtOAc, and DCM, and dried in a vacuum oven to afford racemic trans-2-({4′-[(4,6-difluoro-1,3-benzothiazol-2-yl)amino]-1,1-biphenyl-4-yl}-carbonyl)cyclopentanecarboxylic acid (160 mg, 43%). LC-MS ret. time 4.12; m/z 479.3 (MH+); 1H NMR (400 MHz, DMSO-d6) δ 1.55–1.86 (m, 4H), 2.00 (m, 1H), 2.18 (m, 1H), 3.22 (q, 1H), 4.01 (q, 1H), 7.28 (m, 1H), 7.65 (m, 1H), 7.82 (m, 4H), 7.88 (d, 2H), 8.05 (d, 2H), 10.83(s, 1H), 12.23 (s, 1H).

Aufarbeitung

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

Quellen und Nachweise

ORD-Eintrag
ord-110a2526de0c455a8953e7fc8c2033c8
Quelldatensatz
uspto-grants-2006_08
Patentnummer
US07091228B2

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