Triethylamine → N-[(4-Amino-1-isobutyl-6,7-dimethyl-1H-imidazo[4,5-c]pyridin-2-yl)methyl]-N-methoxycyclopropanecarboxamide

HRID 2426369Notes

Reaction equation

HRID 2426369 reaction equation
[CH2:1]([N:5]1[C:13]2[C:12]([CH3:14])=[C:11]([CH3:15])[N:10]=[C:9]([NH2:16])[C:8]=2[N:7]=[C:6]1[CH2:17][NH:18][O:19][CH3:20])[CH:2]([CH3:4])[CH3:3].C(N(CC)CC)C.[CH:28]1([C:31](Cl)=[O:32])[CH2:30][CH2:29]1>ClCCl.C1(C(Cl)=O)CC1>[NH2:16][C:9]1[C:8]2[N:7]=[C:6]([CH2:17][N:18]([O:19][CH3:20])[C:31]([CH:28]3[CH2:30][CH2:29]3)=[O:32])[N:5]([CH2:1][CH:2]([CH3:4])[CH3:3])[C:13]=2[C:12]([CH3:14])=[C:11]([CH3:15])[N:10]=1

Participants

6

Reactant 3

HCID 8471Triethylamine2×HCID 77637Cyclopropanecarbonyl chloride2×HCID 119562431-isobutyl-2-[(methoxyamino)methyl]-6,7-dimethyl-1H-imidazo[4,5-c]pyridin-4-amine

Product 1

HCID 11956245N-[(4-Amino-1-isobutyl-6,7-dimethyl-1H-imidazo[4,5-c]pyridin-2-yl)methyl]-N-methoxycyclopropanecarboxamideYield 44.3%

Reagents, catalysts & solvents 2

HCID 77637Cyclopropanecarbonyl chlorideCatalystHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
-5 °C

Procedure

Under a nitrogen atmosphere, 1-isobutyl-2-[(methoxyamino)methyl]-6,7-dimethyl-1H-imidazo[4,5-c]pyridin-4-amine (0.53 g, 1.91 mmol) was dissolved in dichloromethane (19 mL) and cooled to −5° C. Triethylamine (293 uL, 2.10 mmol) was added followed by dropwise addition of cyclopropane carbonyl chloride (173 uL, 1.91 mmol). The solution was allowed to stir at RT for 2 hours, then cooled back to −5° C. More triethylamine (38 uL, 0.27 mmol) and cyclopropane carbonyl chloride (23 uL, 0.25 mmol) were added and the reaction was allowed to stir at 0° C. for 45 minutes. More cyclopropane carbonyl chloride (5 uL, 0.06 mmol) was added and stirring continued for another 30 minutes. Dichloromethane (100 mL) was added and the solution was washed successively with saturated aqueous sodium bicarbonate (30 mL), water (3×25 mL), and brine (20 mL), dried over sodium sulfate, filtered and concentrated under reduced pressure. The crude product was purified by HPFC eluting with a gradient of 0-35% CMA in chloroform and then recrystallized from ethyl acetate/hexanes to provide 292 mg of pure product as an off-white powder, mp 135.0-137.0° C. Anal. Calcd for C18H27N5O2 C, 62.59; H, 7.88; N, 20.27. Found: C, 62.68; H, 7.82; N, 19.93.

Workup

  1. temperaturecooled back to −5° C
  2. stirringto stir at 0° C. for 45 minutes
  3. stirringstirring
  4. waitcontinued for another 30 minutes
  5. washthe solution was washed successively with saturated aqueous sodium bicarbonate (30 mL), water (3×25 mL), and brine (20 mL)
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe crude product was purified by HPFC
  10. washeluting with a gradient of 0-35% CMA in chloroform
  11. customrecrystallized from ethyl acetate/hexanes

Sources & evidence

ORD record
ord-e2641039fa064fdea75fd6be3662503e
Source dataset
uspto-grants-2011_06
Patent number
US07968563B2

Reaction notes

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