2-Cyclopentene-1-ol → 3-(2-(4-(Benzo[D]thiazol-2-ylamino)phenoxy)pyridin-3-YL)cyclopentanone

HRID 1880173Notes

Reaction equation

HRID 1880173 reaction equation
I[C:2]1[C:3]([O:8][C:9]2[CH:14]=[CH:13][C:12]([NH:15][C:16]3[S:17][C:18]4[CH:24]=[CH:23][CH:22]=[CH:21][C:19]=4[N:20]=3)=[CH:11][CH:10]=2)=[N:4][CH:5]=[CH:6][CH:7]=1.[CH:25]1([OH:30])[CH2:29][CH2:28][CH:27]=[CH:26]1.C([O-])(=O)C.[K+]>[Cl-].C([N+](CCCC)(CCCC)CCCC)CCC.C(#N)C.O.ClCCl.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[S:17]1[C:18]2[CH:24]=[CH:23][CH:22]=[CH:21][C:19]=2[N:20]=[C:16]1[NH:15][C:12]1[CH:13]=[CH:14][C:9]([O:8][C:3]2[C:2]([CH:27]3[CH2:28][CH2:29][C:25](=[O:30])[CH2:26]3)=[CH:7][CH:6]=[CH:5][N:4]=2)=[CH:10][CH:11]=1

Participants

9

Reactant 3

HCID 2201642-Cyclopentene-1-olHCID 517044Potassium AcetateHCID 59327141N-(4-(3-Iodopyridin-2-yloxy)phenyl)benzo[D]thiazol-2-amine

Product 1

HCID 593270863-(2-(4-(Benzo[D]thiazol-2-ylamino)phenoxy)pyridin-3-YL)cyclopentanone

Reagents, catalysts & solvents 5

HCID 70681Tetrabutylammonium ChlorideCatalystHCID 167845palladium(II) acetateCatalyst2×HCID 962WaterSolventHCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
90 °C

Procedure

A suspension of N-(4-(3-iodopyridin-2-yloxy)phenyl)benzo[d]thiazol-2-amine (493 mg, 1.107 mmol), cyclopent-2-enol (373 mg, 4.43 mmol), potassium acetate (217 mg, 2.214 mmol), tetrabutylammonium chloride (338 mg, 1.218 mmol) and Palladium (II) acetate (24.86 mg, 0.111 mmol) in acetonitrile (3 mL) and water (0.300 mL) was degassed and backfilled with argon. The reaction was heated to 90° C. for 18 h. Palladium (II) acetate (24.86 mg, 0.111 mmol) was added, and the reaction was capped, degassed and filled with argon, and heated to 135° C. in a microwave for 1 h. The crude reaction mixture was diluted with dichloromethane (75 mL) and washed with brine (75 mL), dried over MgSO4, concentrated in vacuo and purified by silica gel chromatography (eluant: 35-50% EtOAc/hexane), affording a white solid. It was further purified on a prep HPLC system (and free-based by partitioning between dichloromethane and saturated sodium bicarbonate solution), affording the product as a white solid. MS (ESI, pos. ion) m/z: 402.1 (M+1). IC50 (uM) +++++.

Workup

  1. customwas degassed
  2. customthe reaction was capped
  3. customdegassed
  4. additionfilled with argon
  5. temperatureheated to 135° C. in a microwave for 1 h
  6. customThe crude reaction mixture
  7. washwashed with brine (75 mL)
  8. dry with materialdried over MgSO4
  9. concentrationconcentrated in vacuo
  10. custompurified by silica gel chromatography (eluant: 35-50% EtOAc/hexane)
  11. customaffording a white solid
  12. customIt was further purified on a prep HPLC system (and free-based by partitioning between dichloromethane and saturated sodium bicarbonate solution)

Sources & evidence

ORD record
ord-8d9d4f04379b4e1b9693836a57c8768a
Source dataset
uspto-grants-2012_11
Patent number
US08318718B2

Reaction notes

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