Chloroacetyl chloride → 1-((1S)-2-{[tert-Butyl(dimethyl)silyl]oxy}-1-methylethyl)-4-chloro-2-(chloromethyl)-6,7-dimethyl-1H-imidazo[4,5-c]pyridine

HRID 1035555Notes

Reaction equation

HRID 1035555 reaction equation
[Si:1]([O:8][CH2:9][C@@H:10]([NH:12][C:13]1[C:18]([CH3:19])=[C:17]([CH3:20])[N:16]=[C:15]([Cl:21])[C:14]=1[NH2:22])[CH3:11])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].C(N(CC)CC)C.[Cl:30][CH2:31][C:32](Cl)=O>ClCCCl>[Si:1]([O:8][CH2:9][C@@H:10]([N:12]1[C:13]2[C:18]([CH3:19])=[C:17]([CH3:20])[N:16]=[C:15]([Cl:21])[C:14]=2[N:22]=[C:32]1[CH2:31][Cl:30])[CH3:11])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 6577Chloroacetyl chlorideHCID 8471TriethylamineHCID 86624129N'-((1S)-2-{[tert-Butyl(dimethyl)silyl]oxy}-1-methylethyl)-2-chloro-5,6-dimethylpyridine-3,4-diamine

Product 1

HCID 866241301-((1S)-2-{[tert-Butyl(dimethyl)silyl]oxy}-1-methylethyl)-4-chloro-2-(chloromethyl)-6,7-dimethyl-1H-imidazo[4,5-c]pyridineYield 13.2%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Conditions

Temperature
0 °C

Procedure

N4-((1S)-2-{[tert-Butyl(dimethyl)silyl]oxy}-1-methylethyl)-2-chloro-5,6-dimethylpyridine-3,4-diamine (2.85 g, 8.29 mmol) was dissolved in 100 mL of dry 1,2-dichloroethane and the solution was cooled to 0° C. as it stirred under an atmosphere of N2. Triethylamine (2.3 mL, 16.58 mmol) and chloroacetyl chloride (0.92 mL, 11.60 mmol) were added sequentially. After 30 minutes, the reaction mixture was allowed to warm to ambient temperature and stirred for 3 days followed by heating to 70° C. for 2 days. The reaction mixture was allowed to cool to ambient temperature and was washed with saturated NaHCO3 solution (2×100 mL) and brine (100 mL). The organic layer was dried over Na2SO4, filtered and concentrated under reduced pressure to afford the crude product as a brown solid. Chromatography (SiO2, 20-50% ethyl acetate/hexanes) gave 1-((1S)-2-{[tert-butyl(dimethyl)silyl]oxy}-1-methylethyl)-4-chloro-2-(chloromethyl)-6,7-dimethyl-1H-imidazo[4,5-c]pyridine (0.44 g) as a yellow oil.

Workup

  1. temperatureto warm to ambient temperature
  2. stirringstirred for 3 days
  3. temperatureby heating to 70° C. for 2 days
  4. temperatureto cool to ambient temperature
  5. washwas washed with saturated NaHCO3 solution (2×100 mL) and brine (100 mL)
  6. dry with materialThe organic layer was dried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customto afford the crude product as a brown solid

Sources & evidence

ORD record
ord-11db143c1cbf49ee8ba7d513e7fc20c5
Source dataset
uspto-grants-2013_10
Patent number
US08546383B2

Reaction notes

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