Hydrochloric Acid → HCID 178490665, compound

HRID 538806Notes

Reaction equation

HRID 538806 reaction equation
[C:1]([C:5]1[S:9][C:8]([NH:10][C:11](=[O:21])[C:12]2[CH:17]=[C:16]([Cl:18])[CH:15]=[CH:14][C:13]=2[O:19][CH3:20])=[N:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2].CC(C)([O-])C.[K+].Cl.Cl[CH2:30][C:31]1[N:32]=[CH:33][S:34][CH:35]=1>CN(C=O)C.C1COCC1.[I-].C([N+](CCCC)(CCCC)CCCC)CCC.C(OCC)(=O)C>[C:1]([C:5]1[S:9]/[C:8](=[N:10]\[C:11](=[O:21])[C:12]2[CH:17]=[C:16]([Cl:18])[CH:15]=[CH:14][C:13]=2[O:19][CH3:20])/[N:7]([CH2:30][C:31]2[N:32]=[CH:33][S:34][CH:35]=2)[CH:6]=1)([CH3:4])([CH3:2])[CH3:3]

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 27632904-(Chloromethyl)-1,3-thiazoleHCID 23665647Potassium tert-butoxideHCID 87094486n-(5-Tert-butylthiazol-2-yl)-5-chloro-2-methoxybenzamide

Product 1

HCID 178490665HCID 178490665, compound

Reagents, catalysts & solvents 3

HCID 67553Tetrabutylammonium IodideCatalystHCID 8857Ethyl AcetateSolventHCID 21974620tetrahydrofuran N,N-dimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of Example 74B (0.75 g, 2.31 mmol) in DMF/THF (1:4, 20 mL) were added potassium tert-butoxide (0.77 g, 6.93 mmol), tetrabutylammonium iodide (0.09, 0.23 mmol) and the commercially available HCl salt of 4-(chloromethyl)thiazole (TCI-US, 0.59 g, 3.46 mmol). The reaction mixture was stirred at 80° C. for 16 hours, cooled, diluted with ethyl acetate (20 mL) and quenched with saturated aqueous NaHCO3 (20 mL). The aqueous layer was extracted with ethyl acetate (2×20 mL). The combined organic layers were washed with water (1×25 mL). The combined organic extracts were dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by column chromatography using an Analogix® Intelliflash280™ (SiO2, 0-100% ethyl acetate in hexanes) to afford the title compound. 1H NMR (300 MHz, dimethylsulfoxide-d6) δ ppm 1.32 (s, 9H), 3.76 (s, 3H), 5.49 (s, 2H), 7.09 (d, J=9.2 Hz, 1H), 7.36 (s, 1H), 7.44 (dd, J=9.0, 2.9 Hz, 1H), 7.57 (d, J=2.0 Hz, 1H), 7.61 (d, J=3.1 Hz, 1H), 9.10 (d, J=2.0 Hz, 1H); MS (ESI+) m/z 422 (M+H)+; Anal. Calculated for C19H20ClN3O2S2: C, 54.08; H, 4.78; N, 9.96. Found: C, 54.10; H, 4.62; N, 9.81.

Workup

  1. temperaturecooled
  2. customquenched with saturated aqueous NaHCO3 (20 mL)
  3. extractionThe aqueous layer was extracted with ethyl acetate (2×20 mL)
  4. washThe combined organic layers were washed with water (1×25 mL)
  5. dry with materialThe combined organic extracts were dried over anhydrous Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified by column chromatography

Sources & evidence

ORD record
ord-0fbb112491a242e290e10d70ee0abbb9
Source dataset
uspto-grants-2014_10
Patent number
US08865753B2

Reaction notes

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