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

HRID 907753

反応式

HRID 907753 の反応式
[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

参加物

5

反応物 4

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

生成物 1

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

反応条件

温度
90 °C

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-fce8fc833c234c03b96c2962a8b7a570
出典データセット
uspto-grants-2011_09
特許番号
US08013166B2

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