Chloroacetyl chloride → N-{7-bromo-4-[(tetrahydro-2H-pyran-4-ylmethyl)amino]quinolin-3-yl}-2-chloroacetamide

HRID 81914Notes

Reaction equation

HRID 81914 reaction equation
[Cl:1][CH2:2][C:3](Cl)=[O:4].[Br:6][C:7]1[CH:16]=[C:15]2[C:10]([C:11]([NH:18][CH2:19][CH:20]3[CH2:25][CH2:24][O:23][CH2:22][CH2:21]3)=[C:12]([NH2:17])[CH:13]=[N:14]2)=[CH:9][CH:8]=1>ClCCl>[Br:6][C:7]1[CH:16]=[C:15]2[C:10]([C:11]([NH:18][CH2:19][CH:20]3[CH2:21][CH2:22][O:23][CH2:24][CH2:25]3)=[C:12]([NH:17][C:3](=[O:4])[CH2:2][Cl:1])[CH:13]=[N:14]2)=[CH:9][CH:8]=1

Participants

4

Reactant 2

HCID 6577Chloroacetyl chloride2×HCID 688209287-bromo-N4-(tetrahydro-2H-pyran-4-ylmethyl)quinoline-3,4-diamine

Product 1

HCID 67280759N-{7-bromo-4-[(tetrahydro-2H-pyran-4-ylmethyl)amino]quinolin-3-yl}-2-chloroacetamideYield 44.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

Chloroacetyl chloride (5.2 mL, 65 mmol) was added to 7-bromo-N4-(tetrahydro-2H-pyran-4-ylmethyl)quinoline-3,4-diamine (55 mmol) dissolved in 273 mL of dichloromethane at 0° C. A solid formed after adding half of the chloroacetyl chloride at which point additional dichloromethane (100 mL) was added. The reaction was stirred for 1 hour at ambient temperature. The yellow suspension was quenched first with aqueous saturated sodium bicarbonate followed by 50% aqueous sodium hydroxide until a pH of 14 was reached. Filtration provided 10 g of N-{7-bromo-4-[(tetrahydro-2H-pyran-4-ylmethyl)amino]quinolin-3-yl}-2-chloroacetamide as a tan solid. The filtrate was placed in a separatory funnel and the layers were separated. The aqueous layer was extracted with additional dichloromethane. The combined organic extracts were combined, dried over sodium sulfate, filtered, and concentrated under reduced pressure to afford additional N-{7-bromo-4-[(tetrahydro-2H-pyran-4-ylmethyl)amino]quinolin-3-yl}-2-chloroacetamide as a yellow oil. The yellow oil was carried forward without further purification assuming a 50% yield (27.3 mmol). The oil was combined with ethanol (100 mL) and triethylamine (7.5 mL, 54 mmol). The resulting yellow solution was refluxed for 2 hours. The reaction was cooled to ambient temperature and the solvent was removed under reduced pressure to provide 7-bromo-2-(chloromethyl)-1-(tetrahydro-2H-pyran-4-ylmethyl)-1H-imidazo[4,5-c]quinoline as a brown oil that was used without further purification assuming quantitative yield.

Workup

  1. customA solid formed
  2. additionwas added
  3. customThe yellow suspension was quenched first with aqueous saturated sodium bicarbonate
  4. filtrationFiltration

Sources & evidence

ORD record
ord-9546fee4fc08425eb53c7cd39cd94292
Source dataset
uspto-grants-2014_09
Patent number
US08846710B2

Reaction notes

Loading…