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

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 stir-red 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).

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

ORD 기록

ord-fce8fc833c234c03b96c2962a8b7a570

출처 데이터셋

uspto-grants-2011_09

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US08013166B2