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

HRID 2427393Notes

Reaction equation

HRID 2427393 reaction equation
I[C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]2[S:10][C:11]3[CH:17]=[C:16]([CH3:18])[CH:15]=[CH:14][C:12]=3[N:13]=2)=[CH:4][CH:3]=1.CC1(C)C(C)(C)OB([C:27]2[CH:43]=[CH:42][C:30]([C:31]([C@@H:33]3[CH2:37][CH2:36][CH2:35][C@H:34]3[C:38]([O:40]C)=[O:39])=[O:32])=[CH:29][CH:28]=2)O1.C([O-])(O)=O.[Na+].ClCCl.[OH-].[Na+]>CCOC(C)=O.CCO.C1(C)C=CC=CC=1>[CH3:18][C:16]1[CH:15]=[CH:14][C:12]2[N:13]=[C:9]([NH:8][C:5]3[CH:6]=[CH:7][C:2]([C:27]4[CH:28]=[CH:29][C:30]([C:31]([C@@H:33]5[CH2:37][CH2:36][CH2:35][C@H:34]5[C:38]([OH:40])=[O:39])=[O:32])=[CH:42][CH:43]=4)=[CH:3][CH:4]=3)[S:10][C:11]=2[CH:17]=1

Participants

9

Reactant 5

HCID 6344DichloromethaneHCID 14798Sodium HydroxideHCID 516892Sodium BicarbonateHCID 21985719N-(4-iodophenyl)-6-methyl-1,3-benzothiazol-2-amineHCID 67147282Methyl trans-2-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoyl]cyclopentanecarboxylate

Product 1

HCID 11547033trans-2-({4'-[(6-Methyl-1,3-benzothiazol-2-yl)amino]-1,1'-biphenyl-4-yl}carbonyl)-cyclopentanecarboxylic acidYield 74%

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
85 °C

Procedure

N-(4-iodophenyl)-6-methyl-1,3-benzothiazol-2-amine (0.28 g, 0.78 mmol) and methyl trans-2-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoyl]cyclopentanecarboxylate (0.25 g, 0.71 mmol) were combined in a dry flask under argon. Toluene (15 mL), EtOH (6 mL), and saturated aqueous NaHCO3 (2 mL) were then added, and the resulting solution was degassed by bubbling a flow of argon for 30 minutes. Then [1,1′-bis(diphenylphosphino)-ferrocene]dichloro-palladium (II), complex with dichloromethane (1:1) (57 mg, 0.07 mmol) was added, and the resulting mixture was heated at 85° C. for 16 h. The reaction mixture was then diluted with EtOAc and filtered through a Celite® pad. The solvent was removed by rotary evaporation and the residue was brought up in MeOH. Then 1 N aqueous NaOH (2.0 mL, 2.0 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. Concentrated 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, passed through a pad of silica gel, and concentrated in vacuo. The residue was brought up in EtOAc and the precipitate was collected by filtration, washed with EtOAc, MeOH, and DCM, and dried in a vacuum oven to afford trans-2-({4′-[(6-methyl-1,3-benzothiazol-2-yl)amino]-1,1′-biphenyl-4-yl}carbonyl)-cyclopentanecarboxylic acid (0.24 g, 19%). LC-MS ret. time 3.57; m/z 457.3 (MH+); 1H NMR (400 MHz, DMSO-d6) δ 1.57-1.86 (m, 4H), 2.00 (m, 1H), 2.17 (m, 1H), 2.37 (s, 3H), 3.22 (q, 1H), 4.08 (q, 1H), 7.14 (m, 1H), 7.51 (d, 1H), 7.61 (s, 1H), 7.80 (m, 3H), 7.89 (d, 2H), 8.05 (d, 2H), 10.58 (s, 1H), 12.19 (s, 1H).

Workup

  1. customthe resulting solution was degassed
  2. customby bubbling a flow of argon for 30 minutes
  3. filtrationfiltered through a Celite® pad
  4. customThe solvent was removed by rotary evaporation
  5. concentrationThe reaction mixture was concentrated under reduced pressure
  6. additionConcentrated HCl was added
  7. extractionthe suspension was extracted with EtOAc
  8. washThe combined organic phases were washed with brine
  9. dry with materialdried over sodium sulfate
  10. concentrationconcentrated in vacuo
  11. filtrationthe precipitate was collected by filtration
  12. washwashed with EtOAc, MeOH, and DCM
  13. customdried in a vacuum oven

Sources & evidence

ORD record
ord-c56500553e2245769f32645bf3808de0
Source dataset
uspto-grants-2011_06
Patent number
US07968576B2

Reaction notes

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