Hydrochloric Acid → HCID 178487682, compound

HRID 2405841Notes

Reaction equation

HRID 2405841 reaction equation
[C:1]([C:4]1[C:9]([NH:10][C:11]([C:13]2[N:14]=[C:15]([NH:18][CH:19]([CH3:21])[CH3:20])[O:16][CH:17]=2)=O)=[C:8]([Cl:22])[C:7]([O:23][CH3:24])=[CH:6][CH:5]=1)(=[O:3])[CH3:2].[H-].[Na+].C1COCC1.Cl>C1(C)C=CC=CC=1.CCOCC.O.CC#N>[Cl:22][C:8]1[C:7]([O:23][CH3:24])=[CH:6][CH:5]=[C:4]2[C:9]=1[N:10]=[C:11]([C:13]1[N:14]=[C:15]([NH:18][CH:19]([CH3:21])[CH3:20])[O:16][CH:17]=1)[CH:2]=[C:1]2[OH:3]

Participants

9

Reactant 4

HCID 313Hydrochloric AcidHCID 8028TetrahydrofuranHCID 24758Sodium hydride2×HCID 57785336HCID 57785336, compound

Product 1

HCID 178487682HCID 178487682, compoundYield 102.7%

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 1140TolueneSolventHCID 3283Diethyl EtherSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
110 °C

Procedure

2-Isopropylamino-oxazole-4-carboxylic acid (6-acetyl-2-chloro-3-methoxyphenyl)amide (863 mg, 2.45 mmol) was suspended in toluene (20 ml). NaH (147.3 mg, 3.7 mmol) was added to the vigorously stirred mixture while monitoring H2 evolution. The reaction was refluxed (110° C.) for 3 h. After cooling, additional NaH (approx 80 mg) was carefully added, followed by 20 mL of THF to aid solubility. The mixture was heated for an additional 2 h. After cooling to room temperature, the reaction mixture was acidified to pH 2 with conc. HCl. The slurry was stirred for 1 h at rt, then 10 mL of CH3CN was added, followed by 5 mL H2O and 20 mL of ether. The mixture was stirred for another 30 min, and then the solids were collected by filtration and washed with ether and hexane. The wet cake was dried under high vacuum to a constant weight to provide 8-chloro-2-(2-isopropylaminooxazol-4-yl)-7-methoxy-quinolin-4-ol (840 mg, 100% yield) that was used without further purification. LCMS found 334 [M+H]+.

Workup

  1. temperatureAfter cooling
  2. temperatureThe mixture was heated for an additional 2 h
  3. temperatureAfter cooling to room temperature
  4. stirringThe mixture was stirred for another 30 min
  5. filtrationthe solids were collected by filtration
  6. washwashed with ether and hexane
  7. customThe wet cake was dried under high vacuum to a constant weight

Sources & evidence

ORD record
ord-e19a641f816e4169b47f1d6fadfedf9b
Source dataset
uspto-grants-2014_08
Patent number
US08809267B2

Reaction notes

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