4-Toluenesulfonyl chloride → HCID 86612244, compound

HRID 1623095Notes

Reaction equation

HRID 1623095 reaction equation
ClC1C=C(C=CC=1)C(OO)=O.[CH3:12][O:13][N:14]=[CH:15][CH2:16][CH2:17][CH2:18][N:19]1[C:31]2[C:30]3[N:29]=[CH:28][CH:27]=[CH:26][C:25]=3[N:24]=[CH:23][C:22]=2[N:21]=[C:20]1[CH2:32][CH2:33][CH3:34].[OH-].[NH4+:36].C1(C)C=CC(S(Cl)(=O)=O)=CC=1>C(Cl)(Cl)Cl>[CH3:12][O:13][N:14]=[CH:15][CH2:16][CH2:17][CH2:18][N:19]1[C:31]2[C:30]3[N:29]=[CH:28][CH:27]=[CH:26][C:25]=3[N:24]=[C:23]([NH2:36])[C:22]=2[N:21]=[C:20]1[CH2:32][CH2:33][CH3:34]

Participants

6

Reactant 4

HCID 73974-Toluenesulfonyl chlorideHCID 14923Ammonium HydroxideHCID 70297m-Chloroperbenzoic acid2×HCID 86612243HCID 86612243, compound

Product 1

HCID 86612244HCID 86612244, compound

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Procedure

3-Chloroperoxybenzoic acid (3.43 g of 70%, 19.9 mmol, 2.0 eq) was added to a solution of 4-(2-propyl-1H-imidazo[4,5-c][1,5]naphthyridin-1-yl)butyraldehyde O-methyloxime (3.1 g, 9.96 mmol, 1.0 eq) in chloroform (45 mL). The reaction was stirred at ambient temperature for one hour. Analysis by thin layer chromatography indicated that the reaction was incomplete so additional 3-chloroperoxybenzoic acid (0.70 g) was added. After one additional hour of string, ammonium hydroxide (12 mL of 15M) and p-toluenesulfonyl chloride (2.1 g, 11 mmol, 1.1 eq) were added dropwise. The reaction mixture was stirred for an additional hour, filtered to remove the resulting white solid, and diluted with dichloromethane (60 mL) and saturated aqueous sodium bicarbonate (75 mL). The phases were separated and the aqueous phase was extracted with dichloromethane (2×20 mL). The combined organics were dried over magnesium sulfate, filtered, and then concentrated under reduced pressure to provide a dark orange oil. The material was triturated with acetonitrile to afford 0.94 g of 4-(4-amino-2-propyl-1H-imidazo[4,5-c][1,5]naphthyridin-1-yl)butyraldehyde O-methyloxime as a tan solid material. The filtrate from the trituration was purified by BIOTAGE HORIZON High-Performance Flash Chromatography (HPFC) instrument (eluting with chloroform/methanol/ammonium hydroxide (CMA) (80/18/2):chloroform ranging in ratios from 0:100 to 25:75) to provide an additional 0.84 g of product.

Workup

  1. additionwas added
  2. stirringThe reaction mixture was stirred for an additional hour
  3. filtrationfiltered
  4. customto remove the resulting white solid
  5. additiondiluted with dichloromethane (60 mL) and saturated aqueous sodium bicarbonate (75 mL)
  6. customThe phases were separated
  7. extractionthe aqueous phase was extracted with dichloromethane (2×20 mL)
  8. dry with materialThe combined organics were dried over magnesium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated under reduced pressure
  11. customto provide a dark orange oil
  12. customThe material was triturated with acetonitrile

Sources & evidence

ORD record
ord-6d7043ff004d4b4694507a11f42e0d99
Source dataset
uspto-grants-2014_07
Patent number
US08778963B2

Reaction notes

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