Sodium Hydroxide → trans-2-({4'-[(6-Chloro-1,3-benzothiazol-2-yl) amino]-1,1'-biphenyl-4-yl}carbonyl)cyclobutanecarboxylic acid

HRID 9611

Reaction equation

HRID 9611 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[CH:33]=[C:32]([Cl:34])[CH:31]=[CH:30][C:28]=2[N:29]=1.[OH-].[Na+]>C(O)CCC>[Cl:34][C:32]1[CH:31]=[CH:30][C:28]2[N:29]=[C:25]([NH:1][C:2]3[CH:7]=[CH:6][C:5]([C:8]4[CH:13]=[CH:12][C:11]([C:14]([C@@H:16]5[CH2:19][CH2:18][C@H:17]5[C:20]([OH:22])=[O:21])=[O:15])=[CH:10][CH:9]=4)=[CH:4][CH:3]=3)[S:26][C:27]=2[CH:33]=1

Participants

5

Reactant 3

HCID 14798Sodium HydroxideHCID 771762,6-DichlorobenzothiazoleHCID 58681294Methyl trans-2-[(4'-amino-1,1'-biphenyl-4-yl)carbonyl]cyclobutanecarboxylate

Product 1

HCID 58681281trans-2-({4'-[(6-Chloro-1,3-benzothiazol-2-yl) amino]-1,1'-biphenyl-4-yl}carbonyl)cyclobutanecarboxylic acidYield 10.8%

Reagents, catalysts & solvents 1

HCID 2631-ButanolSolvent

Conditions

Temperature
90 °C

Procedure

To a solution of methyl trans-2-[(4′-amino-1,1′-biphenyl-4-yl) carbonyl]cyclobutane-carboxylate (100 mg, 0.32 mmol) in n-butanol (15 mL) was added 2,6-dichloro-1,3-benzothiazole (396 mg, 1.94 mmol), and 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 (1.0 mL, 1.0 mmol) was added to the suspension, and the reaction mixture was stirred at 50° C. overnight. The reaction mixture was concentrated, and the residue was suspended in water. Concentrated HCl was added to adjust the acidity to pH 1, and the precipitate that formed was collected by filtration, washed with water and MeOH, and dried in a vacuum oven to give trans-2-({4′-[(6-chloro-1,3-benzothiazol-2-yl) amino]-1,1′-biphenyl-4-yl}carbonyl)cyclobutanecarboxylic acid (16 mg, 10%). LC-MS ret. time 3.69; m/z 463.1 (MH+); 1H NMR (400 MHz, DMSO-d6) δ 2.01–2.23 (m, 3 H), 2.32 (m, 1H), 3.43 (m, 1H), 4.32 (m, 1H), 7.35 (m, 1H), 7.31 (m, 1H), 7.62 (d, 1H), 7.81 (m, 4H), 7.90 (d, 2H), 7.98 (m, 3H), 10.77 (s, 1H), 12.29 (s, 1H).

Workup

  1. customthe resulting reaction mixture
  2. customThe mixture was evaporated to dryness
  3. concentrationThe reaction mixture was concentrated
  4. additionConcentrated HCl was added
  5. customthe precipitate that formed
  6. filtrationwas collected by filtration
  7. washwashed with water and MeOH
  8. customdried in a vacuum oven

Sources & evidence

ORD record
ord-a7d13e8b265d44deab7c9b18657558b9
Source dataset
uspto-grants-2006_08
Patent number
US07091228B2

Linked notes

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