Phosphorus oxychloride → 4-Chloro-7-methoxy-2-[4-(propan-2-yl)-1,3-thiazol-2-yl]quinoline

HRID 643856Notes

Reaction equation

HRID 643856 reaction equation
[CH:1]([C:4]1[N:5]=[C:6]([C:9]2[CH:18]=[C:17](O)[C:16]3[C:11](=[CH:12][C:13]([O:20][CH3:21])=[CH:14][CH:15]=3)[N:10]=2)[S:7][CH:8]=1)([CH3:3])[CH3:2].P(Cl)(Cl)([Cl:24])=O>>[Cl:24][C:17]1[C:16]2[C:11](=[CH:12][C:13]([O:20][CH3:21])=[CH:14][CH:15]=2)[N:10]=[C:9]([C:6]2[S:7][CH:8]=[C:4]([CH:1]([CH3:3])[CH3:2])[N:5]=2)[CH:18]=1

Participants

3

Reactant 2

HCID 24813Phosphorus oxychloride2×HCID 178487691HCID 178487691, compound

Product 1

HCID 224992914-Chloro-7-methoxy-2-[4-(propan-2-yl)-1,3-thiazol-2-yl]quinolineYield 62%

Conditions

Temperature
100 °C

Procedure

2-(4-Isopropylthiazol-2-yl)-7-methoxyquinolin-4-ol, prepared as described in WO00/59929, (3.6 g) was mixed with 20 ml of phosphorus oxychloride and heated at 100° C. for 40 min. Reaction was monitored by LC-MS. After 40 min of heating the excess of phosphorus oxychloride was removed by rotary evaporation. The residual oil was mixed with sat. sodium bicarbonate solution and extracted into ether (3×70 ml). The combined organic extracts were washed with brine, dried over magnesium sulfate, concentrated by rotary evaporation and passed through short pad of silica (hexane) to give the title compound as a white powder 3.6 g (yield 62%).

Workup

  1. customReaction
  2. customwas removed by rotary evaporation
  3. additionThe residual oil was mixed with sat. sodium bicarbonate solution
  4. extractionextracted into ether (3×70 ml)
  5. washThe combined organic extracts were washed with brine
  6. dry with materialdried over magnesium sulfate
  7. concentrationconcentrated by rotary evaporation

Sources & evidence

ORD record
ord-40c766ed471a471e8c3e0f3259b5d04a
Source dataset
uspto-grants-2010_04
Patent number
US07700552B2

Reaction notes

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