Hydrochloric Acid → HCID 25154626, compound

HRID 2077599Notes

Reaction equation

HRID 2077599 reaction equation
[Cl:1][C:2]1[N:7]=[CH:6][C:5]([C:8]2[CH:20]=[CH:19][C:11]3[N:12]=[C:13]([NH:15][C:16](=[O:18])[CH3:17])[S:14][C:10]=3[CH:9]=2)=[CH:4][C:3]=1[O:21][CH2:22][O:23]CCOC.Cl.[CH3:29]C(OC(C)=O)=O>>[C:22]([O:21][C:3]1[C:2]([Cl:1])=[N:7][CH:6]=[C:5]([C:8]2[CH:20]=[CH:19][C:11]3[N:12]=[C:13]([NH:15][C:16](=[O:18])[CH3:17])[S:14][C:10]=3[CH:9]=2)[CH:4]=1)(=[O:23])[CH3:29]

Participants

4

Reactant 3

HCID 313Hydrochloric AcidHCID 7918Acetic Anhydride2×HCID 57585046HCID 57585046, compound

Product 1

HCID 25154626HCID 25154626, compoundYield 52%

Conditions

Temperature
120 °C

Procedure

A 10 mL flask was charged with N-(6-(6-chloro-5-((2-methoxyethoxy)methoxy)pyridin-3-yl)benzo[d]thiazol-2-yl)acetamide (0.0683 g, 0.167 mmol), 5 mL TFE, a stirbar and 2.0 M HCl (0.251 ml, 0.502 mmol). The flask was fitted with a reflux condenser, heated in a 120° C. oil bath for 45 minutes and cooled. The solvent was removed in vacuo, and the residue was suspended in 3 mL EtOH, and heated with a 120° C. oil bath for 5 minutes and cooled. HPLC-MS showed that a significant amount of de-acetylation had occurred. The solvent was removed in vacuo, the residue was dissolved in 3 mL dry pyridine, and stirred under an Ar atmosphere with 100 mg 5 {acute over (Å)} activated powdered molecular sieves for 1 h. The slurry was filtered, and the molecular sieves were washed with 1 mL dy pyridine. The filtrate was treated with Ac2O (0.0474 ml, 0.502 mmol) and the flask was heated using a 70° C. oil bath for 3 h. An additional aliquot of Ac2O (0.0474 ml, 0.502 mmol) was added, and heating was continued for 2 h. The solution was cooled, and the solvent was removed in vacuo. The residue was treated with 3 mL dry TFE and concentrated in vacuo, and evacuated to 0.4 mm Hg over night. The solids were suspended in 2 mL 10% aqueous EtOH, and filtered. The solids were collected using a glass frit under position pressure nitrogen, and washed with EtOH (2×1 mL). The precipitate was initially dried under a stream of nitrogen, and then at 60° C. and <1 mm Hg for 1 h to afford 5-(2-acetamidobenzo[d]thiazol-6-yl)-2-chloropyridin-3-yl acetate (0.0314 g, 51.8% yield). 1H NMR (400 MHz, CF3CD2OD) δ ppm 2.15 (s, 3H) 2.25 (s, 3H) 7.50 (dd, J=8.51, 1.56 Hz, 1H) 7.67 (d, J=8.51 Hz, 1H) 7.71 (d, J=2.05 Hz, 1H) 7.84 (d, J=1.17 Hz, 1H) 8.31 (d, J=2.05 Hz, 1H). 13C NMR (101 MHz, CF3CD2OD) δ ppm 20.74 (s, 1 C) 23.29 (s, 1 C) 121.66 (s, 1 C) 122.72 (s, 1 C) 127.52 (s, 1 C) 133.32 (s, 1 C) 133.39 (s, 1 C) 134.61 (s, 1 C) 139.71 (s, 1 C) 144.50 (s, 1 C) 145.96 (s, 1 C) 146.19 (s, 1 C) 149.75 (s, 1 C) 162.07 (s, 1 C) 172.51 (s, 1 C) 173.47 (s, 1 C). HPLC-MS: retention time=1.95 min (97.0%@215 nm; 98.5% @254 nm; m/z=361.9, calculated for C16H12ClN3O3S+H+=362.0).

Workup

  1. customThe flask was fitted with a reflux condenser
  2. temperaturecooled
  3. customThe solvent was removed in vacuo
  4. temperatureheated with a 120° C. oil bath for 5 minutes
  5. temperaturecooled
  6. customThe solvent was removed in vacuo
  7. dissolutionthe residue was dissolved in 3 mL dry pyridine
  8. customfor 1 h
  9. filtrationThe slurry was filtered
  10. washthe molecular sieves were washed with 1 mL dy pyridine
  11. temperaturethe flask was heated
  12. customusing a 70° C.
  13. customfor 3 h
  14. temperatureheating
  15. temperatureThe solution was cooled
  16. customthe solvent was removed in vacuo
  17. additionThe residue was treated with 3 mL
  18. customdry TFE
  19. concentrationconcentrated in vacuo
  20. customevacuated to 0.4 mm Hg over night
  21. filtrationfiltered
  22. customThe solids were collected
  23. washwashed with EtOH (2×1 mL)
  24. customThe precipitate was initially dried under a stream of nitrogen

Sources & evidence

ORD record
ord-d618813dbd064f94b25bbc9d07a68710
Source dataset
uspto-grants-2011_04
Patent number
US07928140B2

Reaction notes

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