Chloroacetyl chloride → HCID 66958458, compound

HRID 1907933Notes

Reaction equation

HRID 1907933 reaction equation
C(N(CC)CC)C.[C:8]([O:12][C:13](=[O:30])[NH:14][CH2:15][CH2:16][CH2:17][NH:18][C:19]1[C:28]2[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=2)[N:22]=[CH:21][C:20]=1[NH2:29])([CH3:11])([CH3:10])[CH3:9].[Cl:31][CH2:32][C:33](Cl)=O>ClCCl.CO>[C:8]([O:12][C:13](=[O:30])[NH:14][CH2:15][CH2:16][CH2:17][N:18]1[C:19]2[C:28]3[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=3[N:22]=[CH:21][C:20]=2[N:29]=[C:33]1[CH2:32][Cl:31])([CH3:11])([CH3:9])[CH3:10]

Participants

6

Reactant 3

HCID 6577Chloroacetyl chlorideHCID 8471TriethylamineHCID 66958404HCID 66958404, compound

Product 1

HCID 66958458HCID 66958458, compoundYield 55.5%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent2×

Procedure

Triethylamine (9 mL, 64.7 mmol) was added to a solution of tert-butyl[3-(3-aminoquinolin-4-ylamino)propyl]carbamate (13.65 g, 43.1 mmol) in dichloromethane (150 mL). Chloroacetyl chloride (3.8 mL, 47.5 mmol) was added dropwise over a period of 10 minutes. The reaction mixture was stirred at ambient temperature over the weekend and then concentrated under reduced pressure. The residue was partitioned between ethyl acetate (100 mL) and 1:1 water:saturated aqueous sodium bicarbonate. The organic layer was washed with brine (100 mL). The combined aqueous layers were extracted with ethyl acetate (2×100 mL). The combined organics were dried over magnesium sulfate, filtered, and then concentrated under reduced pressure to provide 14.1 g of crude product as a brown foam. The foam was dissolved in a mixture of dichloromethane (15 mL) and methanol (0.5 mL). The solution was divided and loaded onto two FLASH 40+M silica cartridges (90 g). The cartridges were eluted sequentially with 1 L 1:1 ethyl acetate:hexanes, 5% methanol in 1:1 ethyl acetate:hexanes, and 10% methanol in 1:1 ethyl acetate:hexanes. The fractions containing product were combined and concentrated under reduced pressure to provide 8.96 g of tert-butyl[3-(2-chloromethyl-1H-imidazo[4,5-c]quinolin-1-yl)propyl]carbamate as a light brown foam.

Workup

  1. concentrationconcentrated under reduced pressure
  2. customThe residue was partitioned between ethyl acetate (100 mL) and 1:1 water
  3. washThe organic layer was washed with brine (100 mL)
  4. extractionThe combined aqueous layers were extracted with ethyl acetate (2×100 mL)
  5. dry with materialThe combined organics were dried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customto provide 14.1 g of crude product as a brown foam
  9. washThe cartridges were eluted sequentially with 1 L 1:1 ethyl acetate
  10. additionThe fractions containing product
  11. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-b9e7075ac3f24b5db2749488142f005c
Source dataset
uspto-grants-2013_12
Patent number
US08598192B2

Reaction notes

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