Chloroacetyl chloride → 7-(benzyloxy)-2-(chloromethyl)-1-(tetrahydro-2H-pyran-4-ylmethyl)-1H-imidazo[4,5-c]quinoline

HRID 2426360Notes

Reaction equation

HRID 2426360 reaction equation
[CH2:1]([O:8][C:9]1[CH:18]=[C:17]2[C:12]([C:13]([NH:20][CH2:21][CH:22]3[CH2:27][CH2:26][O:25][CH2:24][CH2:23]3)=[C:14]([NH2:19])[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(N(CC)CC)C.[Cl:35][CH2:36][C:37](Cl)=O>ClCCl>[CH2:1]([O:8][C:9]1[CH:10]=[CH:11][C:12]2[C:13]3[N:20]([CH2:21][CH:22]4[CH2:27][CH2:26][O:25][CH2:24][CH2:23]4)[C:37]([CH2:36][Cl:35])=[N:19][C:14]=3[CH:15]=[N:16][C:17]=2[CH:18]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 6577Chloroacetyl chlorideHCID 8471TriethylamineHCID 670510957-benzyloxy-N4-(tetrahydro-2H-pyran-4-ylmethyl)quinoline-3,4-diamine

Product 1

HCID 672629707-(benzyloxy)-2-(chloromethyl)-1-(tetrahydro-2H-pyran-4-ylmethyl)-1H-imidazo[4,5-c]quinolineYield 190.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a stirred solution of 7-(benzyloxy)-N4-(tetrahydro-2H-pyran-4-ylmethyl)quinoline-3,4-diamine (51.2 g, 0.141 mol) and triethylamine (39.94 g, 0.395 mol) in dichloromethane (410 mL) at 0° C. was added a solution of chloroacetyl chloride (8.67 g, 76.80 mmol) in dichloromethane (40 mL) drop wise by addition funnel. The reaction was stirred at ambient temperature for 17 hours then heated to reflux for 6 hours. The crude mixture was cooled to ambient temperature and partitioned between water and dichloromethane (200 mL). The layers were separated and the aqueous layer extracted with dichloromethane (2×300 mL). The organic layers were combined, washed with brine (2×300 mL), dried over magnesium sulfate, filtered and concentrated under reduced pressure to provide 7-(benzyloxy)-2-(chloromethyl)-1-(tetrahydro-2H-pyran-4-ylmethyl)-1H-imidazo[4,5-c]quinoline (61.7 g) as a brown solid.

Workup

  1. additionwise by addition funnel
  2. temperaturethen heated
  3. temperatureto reflux for 6 hours
  4. custompartitioned between water and dichloromethane (200 mL)
  5. customThe layers were separated
  6. extractionthe aqueous layer extracted with dichloromethane (2×300 mL)
  7. washwashed with brine (2×300 mL)
  8. dry with materialdried over magnesium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-1603adf55972415c84b1fdcc32b569cc
Source dataset
uspto-grants-2011_06
Patent number
US07968563B2

Reaction notes

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