Trifluoroacetic acid → HCID 22348022, compound

HRID 897218Notes

Reaction equation

HRID 897218 reaction equation
C(O[C:6]([N:8]1[CH2:13][CH2:12][CH:11]([NH:14][C:15]2[C:24]3[C:19](=[CH:20][CH:21]=[C:22]([Cl:25])[CH:23]=3)[N:18]([CH2:26][C:27]3[CH:32]=[CH:31][N:30]=[CH:29][CH:28]=3)[C:17](=[O:33])[CH:16]=2)[CH2:10][CH2:9]1)=O)(C)(C)C.FC(F)(F)[C:36]([OH:38])=[O:37]>C(Cl)Cl>[O:37]1[C:20]2[CH:21]=[CH:22][C:23]([CH2:6][N:8]3[CH2:13][CH2:12][CH:11]([NH:14][C:15]4[C:24]5[C:19](=[CH:20][CH:21]=[C:22]([Cl:25])[CH:23]=5)[N:18]([CH2:26][C:27]5[CH:32]=[CH:31][N:30]=[CH:29][CH:28]=5)[C:17](=[O:33])[CH:16]=4)[CH2:10][CH2:9]3)=[CH:24][C:19]=2[O:38][CH2:36]1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 69738349HCID 69738349, compound

Product 1

HCID 22348022HCID 22348022, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
50 °C

Procedure

4-(6-Chloro-2-oxo-1-pyridin-4-ylmethyl-1,2-dihydroquinolin-4-ylamino)-piperidine-1-carboxylic acid t-butyl ester (1.22 g, 2.6 mmol) was dissolved in DCM (10 mL) and treated with trifluoroacetic acid (5 mL). The solution was stirred for 15 minutes before evaporating under reduced pressure. The crude amine was dissolved in acetone (25 mL), treated with cesium carbonate (1.26 g) and stirred for 15 minutes prior to addition of piperonyl chloride (50% wt solution in DCM, 1.4 mL). The mixture was heated to 50° C. for 8 hours at which time LC/MS analysis indicated the reaction was complete. The reaction was diluted with ethyl acetate and washed with 1 N NaOH. The organic layer was dried with sodium sulfate and concentrated to give the crude product which was purified by silica chromatography using DCM and methanol eluent to give the title compound (0.91 g). 1H NMR (300 MHz, CDCl3) δ ppm 2.07 (2H, m), 2.23 (2H, m), 2.67 (2H, m), 3.19 (2H, m), 3.67 (1H, m), 3.81 (2H, s), 5.44 (3H, br s), 5.81 (1H, s), 5.95 (2H, s), 6.77 (1H, d, J=7.91 Hz), 6.93 (1H, m), 7.04 (4H, m), 7.30 (1H, m), 7.81 (1H, m), 8.48 (2H, m).

Workup

  1. custombefore evaporating under reduced pressure
  2. dissolutionThe crude amine was dissolved in acetone (25 mL)
  3. additiontreated with cesium carbonate (1.26 g)
  4. stirringstirred for 15 minutes
  5. additionto addition of piperonyl chloride (50% wt solution in DCM, 1.4 mL)
  6. additionThe reaction was diluted with ethyl acetate
  7. washwashed with 1 N NaOH
  8. dry with materialThe organic layer was dried with sodium sulfate
  9. concentrationconcentrated
  10. customto give the crude product which
  11. customwas purified by silica chromatography

Sources & evidence

ORD record
ord-a0396d0245a9461da84bbc3fe38ba37a
Source dataset
uspto-grants-2005_07
Patent number
US06921821B2

Reaction notes

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