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

반응식

HRID 9613 반응식
[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

참가 물질

5

반응물 4

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

생성물 1

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

반응 조건

온도
90 °C

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-110a2526de0c455a8953e7fc8c2033c8
출처 데이터셋
uspto-grants-2006_08
특허 번호
US07091228B2

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