Hydrochloric Acid → HCID 178456840, compound

HRID 1893692Notes

Reaction equation

HRID 1893692 reaction equation
Cl[CH2:2][CH2:3][N:4]1[CH2:9][CH2:8]O[CH2:6][CH2:5]1.[I-].[Na+].[C:12](=O)([O-])[O-].[Cs+].[Cs+].[Cl:18][C:19]1[C:20]([OH:39])=[CH:21][CH:22]=[C:23]2[C:28]=1[N:27]=[C:26]([C:29]1[N:30]=[C:31]([NH:34][CH:35]([CH3:37])[CH3:36])[O:32][CH:33]=1)[CH:25]=[C:24]2[OH:38].Cl>CN(C=O)C>[Cl:18][C:19]1[C:20]([O:39][CH2:2][CH2:3][N:4]2[CH2:9][CH2:8][CH2:12][CH2:6][CH2:5]2)=[CH:21][CH:22]=[C:23]2[C:28]=1[N:27]=[C:26]([C:29]1[N:30]=[C:31]([NH:34][CH:35]([CH3:36])[CH3:37])[O:32][CH:33]=1)[CH:25]=[C:24]2[OH:38]

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 5238Sodium IodideHCID 10796Cesium carbonateHCID 767274-(2-Chloroethyl)morpholineHCID 178456839HCID 178456839, compound

Product 1

HCID 178456840HCID 178456840, compoundYield 62.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

The hydrochloride salt of 4-(2-chloroethyl)morpholine (1.4 g, 7.2 mmol), sodium iodide 0.2 g, 1.3 mmol), and cesium carbonate (5.4 g, 16.4 mmol) were combined in DMF (25 mL) and stirred at rt for 5 min. 8-Chloro-2-(2-isopropylamino-oxazol-4-yl)-quinoline-4,7-diol (2.1 g, 6.6 mmol) was diluted in DMF (25 mL) and added to the reaction solution. After 5 min at rt, the reaction was warmed to 65° C. for 5 h. A small amount of conc. HCl (5-6 pipette drops) was added and the reaction concentrated in vacuo. The residue was taken up in water and MeOH and filtered through a C18 column to remove salts, first eluting with water then with MeOH to elute the desired compound. Following concentration of combined organics in vacuo, the resulting residue was purified by reverse phase HPLC to produce 1.79 g (51% yield) of 8-chloro-2-(2-isopropylamino-oxazol-4-yl)-7-(2-piperidin-1-yl-ethoxy)-quinolin-4-ol. LCMS found 433.3 [M+H]+.

Workup

  1. additionadded to the reaction solution
  2. waitAfter 5 min at rt
  3. temperaturethe reaction was warmed to 65° C. for 5 h
  4. concentrationthe reaction concentrated in vacuo
  5. filtrationMeOH and filtered through a C18 column
  6. customto remove salts
  7. washfirst eluting with water
  8. washwith MeOH to elute the desired compound
  9. customthe resulting residue was purified by reverse phase HPLC

Sources & evidence

ORD record
ord-6b568ddd945948428a0400c3cd6ba7f5
Source dataset
uspto-grants-2013_08
Patent number
US08513186B2

Reaction notes

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