4-Toluenesulfonyl chloride → HCID 69507356, compound

HRID 1623104Notes

Reaction equation

HRID 1623104 reaction equation
ClC1C=C(C=CC=1)C(OO)=O.[CH2:12]([C:16]1[N:17]([CH2:29][CH2:30][CH2:31][C:32](=[O:34])[CH3:33])[C:18]2[C:27]3[N:26]=[CH:25][CH:24]=[CH:23][C:22]=3[N:21]=[CH:20][C:19]=2[N:28]=1)[CH2:13][CH2:14][CH3:15].[OH-].[NH4+:36].C1(C)C=CC(S(Cl)(=O)=O)=CC=1>C(Cl)(Cl)Cl>[NH2:36][C:20]1[C:19]2[N:28]=[C:16]([CH2:12][CH2:13][CH2:14][CH3:15])[N:17]([CH2:29][CH2:30][CH2:31][C:32](=[O:34])[CH3:33])[C:18]=2[C:27]2[N:26]=[CH:25][CH:24]=[CH:23][C:22]=2[N:21]=1

Participants

6

Reactant 4

HCID 73974-Toluenesulfonyl chlorideHCID 14923Ammonium HydroxideHCID 70297m-Chloroperbenzoic acidHCID 69507344HCID 69507344, compound

Product 1

HCID 69507356HCID 69507356, compound

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Procedure

3-Chloroperoxybenzoic acid (70% pure, 5.46 g, 22.16 mmol) (mCPBA) was added to a solution of 5-(2-butyl-1H-imidazo[4,5-c][1,5]naphthyridin-1-yl)pentan-2-one (3.44 g, 11.08 mmol, 1 eq) in chloroform (45 mL), and the reaction was stirred for one hour at ambient temperature and then cooled to 5° C. Ammonium hydroxide (10 mL) and p-toluenesulfonyl chloride (2.32 g, 12.19 mmol, 1.1 eq) were sequentially added and the reaction mixture was stirred at 5-10° C. for 1 hour, filtered, and then diluted with dichloromethane (100 mL) and saturated aqueous sodium bicarbonate (75 mL). The aqueous layer was extracted with dichloromethane (2×30 mL) and the combined organic solutions were dried over magnesium sulfate, filtered, and concentrated under reduced pressure to provide a brown oil. The material was triturated with acetonitrile to afford 1.65 g of 5-(4-amino-2-butyl-1H-imidazo[4,5-c][1,5]naphthyridin-1-yl)pentan-2-one. 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) and subjected to trituration again in acetonitrile to produce an additional 0.240 g of material as an off-white powder, mp 168-169° C. Anal. calcd for C18H23N5O: C, 66.44; H, 7.12; N, 21.52. Found: C, 66.19; H, 7.08; N, 21.22.

Workup

  1. temperaturecooled to 5° C
  2. stirringthe reaction mixture was stirred at 5-10° C. for 1 hour
  3. filtrationfiltered
  4. additiondiluted with dichloromethane (100 mL) and saturated aqueous sodium bicarbonate (75 mL)
  5. extractionThe aqueous layer was extracted with dichloromethane (2×30 mL)
  6. dry with materialthe combined organic solutions were dried over magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customto provide a brown oil
  10. customThe material was triturated with acetonitrile

Sources & evidence

ORD record
ord-fb88e5dd9ecb45c7b0c84221520464bf
Source dataset
uspto-grants-2014_07
Patent number
US08778963B2

Reaction notes

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