Methanol → 4,8-Dichloro-7-(2,2-dimethoxy-ethoxy)-2-(4-isopropyl-thiazol-2-yl)-quinoline

HRID 1422531Notes

Reaction equation

HRID 1422531 reaction equation
[Cl:1][C:2]1[C:3]([O:21][CH2:22][CH:23]([O:26][CH3:27])[O:24][CH3:25])=[CH:4][CH:5]=[C:6]2[C:11]=1[N:10]=[C:9]([C:12]1[S:13][CH:14]=[C:15]([CH:17]([CH3:19])[CH3:18])[N:16]=1)[CH:8]=[C:7]2O.O=P(Cl)(Cl)[Cl:30].CO.C([O-])(O)=O.[Na+]>N1C=CC=CC=1>[Cl:30][C:7]1[C:6]2[C:11](=[C:2]([Cl:1])[C:3]([O:21][CH2:22][CH:23]([O:26][CH3:27])[O:24][CH3:25])=[CH:4][CH:5]=2)[N:10]=[C:9]([C:12]2[S:13][CH:14]=[C:15]([CH:17]([CH3:19])[CH3:18])[N:16]=2)[CH:8]=1

Participants

6

Reactant 4

HCID 887MethanolHCID 24813Phosphorus oxychlorideHCID 516892Sodium BicarbonateHCID 178496099HCID 178496099, compound

Product 1

HCID 582895434,8-Dichloro-7-(2,2-dimethoxy-ethoxy)-2-(4-isopropyl-thiazol-2-yl)-quinolineYield 52%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Conditions

Temperature
80 °C

Procedure

8-Chloro-7-(2,2-dimethoxy-ethoxy)-2-(4-isopropyl-thiazol-2-yl)-quinolin-4-ol (512 mg, 1.25 mmol) was dissolved in pyridine (10 mL). POCl3 (2.30 mL, 25.0 mmol) was added slowly. The reaction was heated at 80° C. for 4 hours. The reaction was cooled to 0° C. and methanol (5 mL) was added. The reaction was neutralized with a sat NaHCO3(aq) solution. The product was extracted with EtOAc (3×20 mL). The combined organics were dried with Na2SO4, filtered and was concentrated. 4,8-dichloro-7-(2,2-dimethoxy-ethoxy)-2-(4-isopropyl-thiazol-2-yl)-quinoline (0.275 mg, 52%) was isolated by silica gel chromatography as a yellow solid.

Workup

  1. temperatureThe reaction was cooled to 0° C.
  2. extractionThe product was extracted with EtOAc (3×20 mL)
  3. dry with materialThe combined organics were dried with Na2SO4
  4. filtrationfiltered
  5. concentrationwas concentrated

Sources & evidence

ORD record
ord-62a6bfac1db34b36bbbfa1667218897d
Source dataset
uspto-grants-2015_01
Patent number
US08927484B2

Reaction notes

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