Pyridine → N-(7-hydroxy-4,5-dihydronaphtho[1,2-d]thiazol-2-yl)benzamide

HRID 1506567Notes

Reaction equation

HRID 1506567 reaction equation
C[O:2][C:3]1[CH:4]=[C:5]2[C:14](=[CH:15][CH:16]=1)[C:9]1[N:10]=[C:11]([NH2:13])[S:12][C:8]=1[CH2:7][CH2:6]2.N1C=CC=CC=1.[C:23](Cl)(=[O:30])[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1.ClCCl>ClC(Cl)C>[OH:2][C:3]1[CH:4]=[C:5]2[C:14](=[CH:15][CH:16]=1)[C:9]1[N:10]=[C:11]([NH:13][C:23](=[O:30])[C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)[S:12][C:8]=1[CH2:7][CH2:6]2

Participants

6

Reactant 4

HCID 1049PyridineHCID 6344DichloromethaneHCID 7412Benzoyl chlorideHCID 6906227-Methoxy-4,5-dihydronaphtho[1,2-d]thiazol-2-amine

Product 1

HCID 86669945N-(7-hydroxy-4,5-dihydronaphtho[1,2-d]thiazol-2-yl)benzamideYield 14.9%

Reagents, catalysts & solvents 1

HCID 63651,1-DichloroethaneSolvent

Conditions

Temperature
45 °C

Procedure

To 7-methoxy-4,5-dihydronaphtho[1,2-d]thiazol-2-amine (17 mg, 0.073 mmol) in dichloroethane (2 mL) and pyridine (17.37 mg, 0.220 mmol) was added benzoyl chloride (0.015 mL, 0.132 mmol) at room temperature. The reaction mixture was heated to 45° C. and stirred for 2 hours. The reaction mixture was cooled to room temperature, 3 ml of dichloromethane was added, and the contents were washed with sat. NaHCO3. The organic layer was dried over Na2SO4 and concentrated and dried under vacuum overnight. The residue was dissolved into 2 ml dichloromethane, cooled to 0° C. using an ice bath. Borontribromide (0.293 mL, 0.293 mmol) was added slowly at 0° C. The reaction mixture was allowed to warm to room temperature slowly and stirred at room temperature for 4 hours. The reaction mixture was quenched with a few drops of MeOH and purified on prep. HPLC (Luna 5 u C18 21.2*100 mm column; 0%-100% 10mins gradient; Solvent A: 10% MeOH-90% H2O-0.1% TFA; Solvent B: 90% MeOH-90% H2O-0.1% TFA). The desired fractions were collected, concentrated and dried overnight to provide 3.5 mg of product. (two-step yield: 11%). LC/MS M+1=323.1. The product had an HPLC retention time=3.31 min. (condition A). 1H NMR (400 MHz, CD3OD) δ ppm 7.99-8.07 (2H, m), 7.63 (2H, d, J=7.48 Hz), 7.57 (2H, d, J=7.70 Hz), 6.70 (2H, s), 2.98 (4H, d, J=4.84 Hz).

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. washthe contents were washed with sat. NaHCO3
  3. dry with materialThe organic layer was dried over Na2SO4
  4. concentrationconcentrated
  5. customdried under vacuum overnight
  6. dissolutionThe residue was dissolved into 2 ml dichloromethane
  7. temperaturecooled to 0° C.
  8. additionBorontribromide (0.293 mL, 0.293 mmol) was added slowly at 0° C
  9. temperatureto warm to room temperature slowly
  10. stirringstirred at room temperature for 4 hours
  11. customThe reaction mixture was quenched with a few drops of MeOH
  12. custompurified on prep
  13. customHPLC (Luna 5 u C18 21.2*100 mm column; 0%-100% 10mins gradient; Solvent A: 10% MeOH-90% H2O-0.1% TFA; Solvent B: 90% MeOH-90% H2O-0.1% TFA)
  14. customThe desired fractions were collected
  15. concentrationconcentrated
  16. customdried overnight

Sources & evidence

ORD record
ord-547b0e8109f8477eae0fa52c2561b970
Source dataset
uspto-grants-2015_12
Patent number
US09216972B2

Reaction notes

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