Dimethylformamide → HCID 86629391, compound

HRID 244845Notes

Reaction equation

HRID 244845 reaction equation
CN(C)C=O.[CH:6]([S:8]([CH3:11])(=[O:10])=[O:9])=[CH2:7].[NH2:12][C:13]1[C:22]2[N:23]=[C:24]([CH2:31][O:32][CH3:33])[N:25]([CH2:26][C:27]([CH3:30])([OH:29])[CH3:28])[C:21]=2[C:20]2[CH:19]=[CH:18][C:17](Br)=[CH:16][C:15]=2[N:14]=1>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1(C)C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C.C(#N)C>[NH2:12][C:13]1[C:22]2[N:23]=[C:24]([CH2:31][O:32][CH3:33])[N:25]([CH2:26][C:27]([CH3:28])([OH:29])[CH3:30])[C:21]=2[C:20]2[CH:19]=[CH:18][C:17]([CH:7]=[CH:6][S:8]([CH3:11])(=[O:10])=[O:9])=[CH:16][C:15]=2[N:14]=1

Participants

7

Reactant 3

HCID 6228DimethylformamideHCID 19354Methyl vinyl sulfoneHCID 21984234HCID 21984234, compound

Product 1

HCID 86629391HCID 86629391, compoundYield 70.2%

Reagents, catalysts & solvents 3

HCID 80271Tri-o-tolylphosphineCatalystHCID 167845palladium(II) acetateCatalystHCID 6342AcetonitrileSolvent

Conditions

Temperature
120 °C

Procedure

A thick walled glass tube, equipped with a stir bar, was charged with palladium (II) acetate (12 mg, 0.05 mmol), acetonitrile (20 mL), N,N-dimethylformamide (15 mL) triethylamine (1.10 mL, 7.92 mmol), tri-o-tolylphosphine (48 mg, 0.16 mmol), methyl vinyl sulfone (294 mg, 2.77 mmol) and 1-[4-amino-7-bromo-2-(methoxymethyl)-1H-imidazo[4,5-c]quinolin-1-yl)-2-methylpropan-2-ol (1.00 g, 2.64 mmol). The reaction mixture was purged with nitrogen. The tube was sealed and heated at 120° C. in an oil bath. The reaction was maintained at 120° C. for 18 hours and then cooled to ambient temperature. The reaction was filtered and the filtrate was concentrated under reduced pressure. The resulting solid was partitioned between chloroform (100 mL) and aqueous 1% sodium carbonate (100 mL). The fractions were separated and the aqueous fraction was extracted with chloroform (5×50 mL). The combined organic fractions were concentrated and purified by chromatography using a HORIZON HPFC system (silica cartridge, eluting with 0-6% gradient of methanol in dichloromethane) to provide 750 mg of 1-{4-amino-2-(methoxymethyl)-7-[2-(methylsulfonyl)ethenyl]-1H-imidazo[4,5-c]quinolin-1-yl}-2-methylpropan-2-ol as a yellow semi-solid. MS (ESI) m/z 405 (M+H)+.

Workup

  1. customA thick walled glass tube, equipped with a stir bar
  2. customThe reaction mixture was purged with nitrogen
  3. customThe tube was sealed
  4. temperatureThe reaction was maintained at 120° C. for 18 hours
  5. temperaturecooled to ambient temperature
  6. filtrationThe reaction was filtered
  7. concentrationthe filtrate was concentrated under reduced pressure
  8. customThe resulting solid was partitioned between chloroform (100 mL) and aqueous 1% sodium carbonate (100 mL)
  9. customThe fractions were separated
  10. extractionthe aqueous fraction was extracted with chloroform (5×50 mL)
  11. concentrationThe combined organic fractions were concentrated
  12. custompurified by chromatography
  13. washa HORIZON HPFC system (silica cartridge, eluting with 0-6% gradient of methanol in dichloromethane)

Sources & evidence

ORD record
ord-e4aa00cbd69c40cd8c580bda4a2cb9fb
Source dataset
uspto-grants-2014_02
Patent number
US08658666B2

Reaction notes

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