Hydrochloric Acid → 2-(4-Isopropylthiazol-2-YL)-7-methoxy-8-methylquinolin-4-OL

HRID 407536Notes

Reaction equation

HRID 407536 reaction equation
CC(C)([O-])C.[K+].[CH:7]([C:10]1[N:11]=[C:12]([C:15]([NH:17][C:18]2[C:23]([CH3:24])=[C:22]([O:25][CH3:26])[CH:21]=[CH:20][C:19]=2[C:27](=[O:29])[CH3:28])=O)[S:13][CH:14]=1)([CH3:9])[CH3:8].O.Cl>C(O)(C)(C)C.CCOCC>[OH:29][C:27]1[C:19]2[C:18](=[C:23]([CH3:24])[C:22]([O:25][CH3:26])=[CH:21][CH:20]=2)[N:17]=[C:15]([C:12]2[S:13][CH:14]=[C:10]([CH:7]([CH3:9])[CH3:8])[N:11]=2)[CH:28]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 962WaterHCID 23665647Potassium tert-butoxideHCID 53482122N-(6-Acetyl-3-methoxy-2-methylphenyl)-4-(propan-2-yl)-1,3-thiazole-2-carboxamide

Product 1

HCID 1784876922-(4-Isopropylthiazol-2-YL)-7-methoxy-8-methylquinolin-4-OLYield 89.2%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 6386tert-ButanolSolvent

Conditions

Temperature
100 °C

Procedure

Potassium tert-butoxide (21.8 g, 195 mmol) was added to a suspension of 2′-[[(4-iso-propylthiazole-2-yl)(oxo)methyl]amino]-4′-methoxy-3′-methylacetophenone (35, 30.8 g, 92.7 mmol) in tert-butanol. The resulting reaction mixtures was heated at 100° C. overnight. Then, the reaction mixture was cooled at room temperature and diluted with ether (100 mL). The precipitate was filtered off and washed with Et2O to give a powder (fraction A). The mother liquor was concentrated in vacuo, triturated in ether, filtered off, and washed with ether to give a powder (fraction 2). Fractions 1 and 2 were mixed and poured into water (250 mL). The pH of the resulting solution was adjusted to 6-7 (control with pH paper) with HCl 1N. The precipitate was filtered off, washed with water and dried. Then, the solid was triturated in diisopropyl ether, filtered off and dried to give 26 g (88%) of the title product 36 as a brownish solid: m/z=315 (M+H)+.

Workup

  1. customThe resulting reaction mixtures
  2. temperatureThen, the reaction mixture was cooled at room temperature
  3. filtrationThe precipitate was filtered off
  4. washwashed with Et2O
  5. customto give a powder (fraction A)
  6. concentrationThe mother liquor was concentrated in vacuo
  7. customtriturated in ether
  8. filtrationfiltered off
  9. washwashed with ether
  10. customto give a powder (fraction 2)
  11. additionFractions 1 and 2 were mixed
  12. filtrationThe precipitate was filtered off
  13. washwashed with water
  14. customdried
  15. customThen, the solid was triturated in diisopropyl ether
  16. filtrationfiltered off
  17. customdried

Sources & evidence

ORD record
ord-b40ddc6456444837aa343cb0f72dc845
Source dataset
uspto-grants-2014_06
Patent number
US08754106B2

Reaction notes

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