2-Cyclopentene-1-ol → HCID 59327086, compound

HRID 410308Notes

Reaction equation

HRID 410308 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 59327086HCID 59327086, compound

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-a4ce46ecd9f643ca9ce6ff91411bf380
Source dataset
uspto-grants-2014_06
Patent number
US08759532B2

Reaction notes

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