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

HRID 30934

Reaction equation

HRID 30934 reaction equation
[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

Participants

6

Reactant 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

Product 1

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

Conditions

Temperature
90 °C

Procedure

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).

Workup

  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

Sources & evidence

ORD record
ord-3284431c08c04504b2c5bdfd4d4ee9f3
Source dataset
uspto-grants-2008_09
Patent number
US07423156B2

Linked notes

Loading…