Propionyl chloride → N-{7-(benzyloxy)-4-[(tetrahydro-2H-pyran-4-ylmethyl)amino]quinolin-3-yl}propanamide dihydrochloride

HRID 540925Notes

Reaction equation

HRID 540925 reaction equation
[CH2:1]([O:8][C:9]1[CH:18]=[C:17]2[C:12]([C:13]([NH:22][CH2:23][CH:24]3[CH2:29][CH2:28][O:27][CH2:26][CH2:25]3)=[C:14]([N+:19]([O-])=O)[CH:15]=[N:16]2)=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:30]([Cl:34])(=[O:33])[CH2:31][CH3:32]>[Pt].C(#N)C>[ClH:34].[ClH:34].[CH2:1]([O:8][C:9]1[CH:18]=[C:17]2[C:12]([C:13]([NH:22][CH2:23][CH:24]3[CH2:29][CH2:28][O:27][CH2:26][CH2:25]3)=[C:14]([NH:19][C:30](=[O:33])[CH2:31][CH3:32])[CH:15]=[N:16]2)=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 2

HCID 62324Propionyl chlorideHCID 67051153(7-benzyloxy-3-nitroquinolin-4-yl)(tetrahydro-2H-pyran-4-ylmethyl)amine

Product 1

HCID 69506972N-{7-(benzyloxy)-4-[(tetrahydro-2H-pyran-4-ylmethyl)amino]quinolin-3-yl}propanamide dihydrochlorideYield 162%

Reagents, catalysts & solvents 2

HCID 23939PlatinumCatalystHCID 6342AcetonitrileSolvent

Conditions

Temperature
8 °C

Procedure

7-(Benzyloxy)-3-nitro-N-(tetrahydro-2H-pyran-4-ylmethyl)quinolin-4-amine (14.1 g, 35.6 mmol) and 5% platinum on carbon (2.0 g) were added to a Parr vessel. The solids were covered with acetonitrile (200 mL) and placed on a hydrogenator. The vessel was degassed three times, then charged with 50 psi (3.4×105 Pa) hydrogen and allowed to shake for 3 hours, replenishing the hydrogen as needed. After 6 hours, the catalyst was removed by filtration through CELITE filter agent. The CELITE was washed with acetonitrile until the filtrate ran clear (˜300 mL). The solvent was evaporated to ½ volume under reduced pressure and cooled to 8° C. Propionyl chloride (3.15 mL, 35.6 mmol) was added dropwise to the solution over 3 minutes. The cooling bath was removed and the reaction was stirred for 16 hours. The resulting precipitate was filtered and washed with acetonitrile. Drying under vacuum for 1 hour afforded 14.2 g of N-{7-(benzyloxy)-4-[(tetrahydro-2H-pyran-4-ylmethyl)amino]quinolin-3-yl}propanamide dihydrochloride as a tan solid.

Workup

  1. customThe vessel was degassed three times
  2. additioncharged with 50 psi (3.4×105 Pa) hydrogen
  3. waitAfter 6 hours
  4. customthe catalyst was removed by filtration through CELITE
  5. filtrationfilter agent
  6. washThe CELITE was washed with acetonitrile until the filtrate
  7. customThe solvent was evaporated
  8. customThe cooling bath was removed
  9. filtrationThe resulting precipitate was filtered
  10. washwashed with acetonitrile
  11. customDrying under vacuum for 1 hour

Sources & evidence

ORD record
ord-dc0f9fab6af84599923af48cbffc4da6
Source dataset
uspto-grants-2014_10
Patent number
US08871782B2

Reaction notes

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