Acetate → HCID 20680718, compound

HRID 651690Notes

Reaction equation

HRID 651690 reaction equation
C(OC(=O)[NH:7][C@H:8]1[CH2:12][CH2:11][N:10]([CH2:13][C:14]2[CH:23]=[C:22]3[C:17]([C:18]([Cl:24])=[CH:19][CH:20]=[N:21]3)=[CH:16][CH:15]=2)[C:9]1=[O:25])(C)(C)C.C1(O)C=CC=CC=1.C([O-])(=O)C.C(#[N:40])C>O>[ClH:24].[NH2:7][C@H:8]1[CH2:12][CH2:11][N:10]([CH2:13][C:14]2[CH:23]=[C:22]3[C:17]([C:18]([NH2:40])=[CH:19][CH:20]=[N:21]3)=[CH:16][CH:15]=2)[C:9]1=[O:25]

Participants

6

Reactant 4

HCID 175AcetateHCID 996PhenolHCID 6342AcetonitrileHCID 70124080HCID 70124080, compound

Product 1

HCID 20680718HCID 20680718, compound

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
100 °C

Procedure

[1-(4-chloroquinolin-7-ylmethyl)-2-oxopyrrolidin-3-(S)-yl]carbamic acid tert-butyl ester (250 mg, 0.665 mmol), phenol (626 mg, 6.65 mmol), and anhydrous acetate (513 mg, 6.65 mmol) are combined and heated at 100° C., with reflux apparatus, under nitrogen overnight. Then the mixture is cooled to room temperature, and acetonitrile (20 mL) and water (20 mL) are added. The solution separates into 2 phases (both containing product), which are concentrated to dryness, and separately purified by reverse phase preparation HPLC with gradient elution 20-40% acetonitrile/water (0.1% trifluoroacetic acid). The product fractions from each run are combined, the solvents are removed in vacuo, and the residue dried under high vacuum overnight. The [1-(4-Aminoquinolin-7-ylmethyl)-2-oxopyrrolidin-3-(S)-yl]carbamic acid tert-butyl ester intermediate is dissolved in methanol, and cooled to 0° C., whilst bubbling dry HCl(g) through the solution until saturated. The reaction mixture is left at room temperature for 2 hours, and concentrated in vacuo. The residue is washed with ether to give the pure product as a colorless powder (170 mg, 0.516 mmol).

Workup

  1. temperaturewith reflux apparatus
  2. customovernight
  3. temperatureThen the mixture is cooled to room temperature
  4. concentrationare concentrated to dryness
  5. customseparately purified by reverse phase preparation HPLC with gradient elution 20-40% acetonitrile/water (0.1% trifluoroacetic acid)
  6. customthe solvents are removed in vacuo
  7. customthe residue dried under high vacuum overnight
  8. dissolutionThe [1-(4-Aminoquinolin-7-ylmethyl)-2-oxopyrrolidin-3-(S)-yl]carbamic acid tert-butyl ester intermediate is dissolved in methanol
  9. temperaturecooled to 0° C.
  10. customwhilst bubbling dry HCl(g) through the solution until saturated
  11. concentrationconcentrated in vacuo
  12. washThe residue is washed with ether

Sources & evidence

ORD record
ord-058d63de09354216917e69219ab0a995
Source dataset
uspto-grants-2001_08
Patent number
US06281227B1

Reaction notes

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