Cesium carbonate → (1R,2R)-2-({4'-[(6-Chloro-1,3-benzothiazol-2-yl)amino]-3'-fluoro-1,1'-biphenyl-4-yl}carbonyl)cyclopentanecarboxylic acid

HRID 2427391

Reaction equation

HRID 2427391 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]([Cl:18])[CH:15]=[CH:14][C:12]=3[N:13]=2)=[C:4]([F:19])[CH:3]=1.B1(B2OC(C)(C)C(C)(C)O2)OC(C)(C)C(C)(C)O1.CC([O-])=O.[K+].Br[C:44]1[CH:59]=[CH:58][C:47]([C:48]([C@@H:50]2[CH2:54][CH2:53][CH2:52][C@H:51]2[C:55]([OH:57])=[O:56])=[O:49])=[CH:46][CH:45]=1.C([O-])([O-])=O.[Cs+].[Cs+]>CN(C=O)C.O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[Cl: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:44]4[CH:45]=[CH:46][C:47]([C:48]([C@@H:50]5[CH2:54][CH2:53][CH2:52][C@H:51]5[C:55]([OH:57])=[O:56])=[O:49])=[CH:58][CH:59]=4)=[CH:3][C:4]=3[F:19])[S:10][C:11]=2[CH:17]=1

Participants

9

Reactant 5

HCID 10796Cesium carbonateHCID 517044Potassium AcetateHCID 2733548Bis(pinacolato)diboraneHCID 23549251trans-2-(4-Bromobenzoyl)cyclopentanecarboxylic acidHCID 23549325N-(4-Iodo-2-fluorophenyl)-6-chloro-1,3-benzothiazol-2-amine

Product 1

HCID 11466071(1R,2R)-2-({4'-[(6-Chloro-1,3-benzothiazol-2-yl)amino]-3'-fluoro-1,1'-biphenyl-4-yl}carbonyl)cyclopentanecarboxylic acidYield 60%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)Catalyst2×HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
85 °C

Procedure

A suspension of N-(4-iodo-2-fluorophenyl)-6-chloro-1,3-benzothiazol-2-amine (200 mg, 0.49 mmol), bis(pinacolato)diboron (130 mg, 0.52 mmol), KOAc (150 mg, 1.48 mmol), and PdCl2(dppf) (30 mg, 0.04 mmol) in DMF (5.0 mL) was degassed by bubbling a flow of nitrogen for 30 minutes. The reaction mixture was heated under nitrogen at 85° C. for 3 h. After the mixture was cooled to rt, (1R,2R)-2-(4-bromobenzoyl)cyclopentanecarboxylic acid (140 mg, 0.49 mmol, >99% ee), Cs2CO3 (400 mg, 1.23 mmol) and PdCl2(dppf) (30 mg, 0.04 mmol) were added, and the reaction mixture was heated at 85° C. under nitrogen for 3 h. TLC analysis showed little starting materials remaining. The reaction mixture was cooled to rt, and diluted with water (50 mL). After the mixture was filtered through a pad of Celite®, 1 N HCl was added to the filtrate to adjust the acidity to pH<3. The solid that formed was collected by filtration, then dissolved in EtOAc (50 mL), and the resulting solution was dried over Na2SO4. Removal of solvent and drying in vacuo provided the desired product (120 mg, 60%, >99% ee). LC-MS m/z 495.3 (MH+), retention time 4.01 min.

Workup

  1. customwas degassed
  2. customby bubbling a flow of nitrogen for 30 minutes
  3. temperatureAfter the mixture was cooled to rt
  4. temperaturethe reaction mixture was heated at 85° C. under nitrogen for 3 h
  5. temperatureThe reaction mixture was cooled to rt
  6. filtrationAfter the mixture was filtered through a pad of Celite®, 1 N HCl
  7. additionwas added to the filtrate
  8. customThe solid that formed
  9. filtrationwas collected by filtration
  10. dissolutiondissolved in EtOAc (50 mL)
  11. dry with materialthe resulting solution was dried over Na2SO4
  12. customRemoval of solvent
  13. customdrying in vacuo

Sources & evidence

ORD record
ord-1adf009dffe94df0a7c1630dce504dad
Source dataset
uspto-grants-2011_06
Patent number
US07968576B2

Linked notes

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