4-Toluenesulfonyl chloride → 1-{[3-(4-fluorophenyl)isoxazol-5-yl]methyl}-5-oxido-1H-imidazo[4,5-c][1,5]naphthyridine

HRID 606073Notes

Reaction equation

HRID 606073 reaction equation
ClC1C=C(C=CC=1)C(OO)=[O:6].[F:12][C:13]1[CH:18]=[CH:17][C:16]([C:19]2[CH:23]=[C:22]([CH2:24][N:25]3[C:37]4[C:36]5[N:35]=[CH:34][CH:33]=[CH:32][C:31]=5[N:30]=[CH:29][C:28]=4[N:27]=[CH:26]3)[O:21][N:20]=2)=[CH:15][CH:14]=1.[OH-].[NH4+].C1(C)C=CC(S(Cl)(=O)=O)=CC=1>ClCCl.C1C=C(Cl)C=C(C(OO)=O)C=1>[F:12][C:13]1[CH:18]=[CH:17][C:16]([C:19]2[CH:23]=[C:22]([CH2:24][N:25]3[C:37]4[C:36]5[N:35]=[CH:34][CH:33]=[CH:32][C:31]=5[N+:30]([O-:6])=[CH:29][C:28]=4[N:27]=[CH:26]3)[O:21][N:20]=2)=[CH:15][CH:14]=1

Participants

7

Reactant 4

HCID 73974-Toluenesulfonyl chlorideHCID 14923Ammonium HydroxideHCID 70297m-Chloroperbenzoic acidHCID 67041334HCID 67041334, compound

Product 1

HCID 670412541-{[3-(4-fluorophenyl)isoxazol-5-yl]methyl}-5-oxido-1H-imidazo[4,5-c][1,5]naphthyridineYield 85.9%

Reagents, catalysts & solvents 2

HCID 70297m-Chloroperbenzoic acidCatalystHCID 6344DichloromethaneSolvent

Procedure

3-Chloroperoxybenzoic acid (mCPBA) (2.4 g of 75% pure material) was added to a suspension of 1-{[3-(4-fluorophenyl)isoxazol-5-yl]methyl}-1H-imidazo[4,5-c][1,5]naphthyridine (2.76 g, 7.99 mmol) in dichloromethane (100 mL). The reaction was stirred at room temperature for 30 minutes; an analysis by TLC then indicated the presence of starting material. Additional mCPBA (0.065 g of 75%) was added, and the reaction was stirred for another 30 minutes and found to be complete by TLC analysis. Concentrated ammonium hydroxide (50 mL) and p-toluenesulfonyl chloride (1.68 g, 8.79 mmol) were sequentially added. The mixture was stirred for 30 minutes. The volatiles were removed under reduced pressure, and 1 N aqueous sodium hydroxide and water were added to the resulting mixture, which was filtered to isolate a solid. The solid was washed with diethyl ether. Additional solid precipitated from the aqueous filtrate, and was isolated by filtration and combined with the first solid to provide 2.48 g of 1-{[3-(4-fluorophenyl)isoxazol-5-yl]methyl}-5-oxido-1H-imidazo[4,5-c][1,5]naphthyridine, which was dissolved in a mixture of methanol (80 mL) and dichloromethane (80 mL). The resulting mixture was heated to 50° C., and concentrated ammonium hydroxide (20 mL) and benzenesulfonyl chloride (1.2 mL, 7.6 mmol) were added. The reaction was heated under a nitrogen atmosphere for one hour, and additional benzenesulfonyl chloride (0.5 mL) was added. The solvents were removed under reduced pressure, and the residue was purified by column chromatography on silica gel (eluting with 2% to 10% CMA in chloroform) followed by recrystallization from acetonitrile to provide 0.612 g of 1-{[3-(4-fluorophenyl)isoxazol-5-yl]methyl}-1H-imidazo[4,5-c][1,5]naphthyridin-4-amine as a white solid, mp 265.0-266.0° C.

Workup

  1. stirringthe reaction was stirred for another 30 minutes
  2. stirringThe mixture was stirred for 30 minutes
  3. customThe volatiles were removed under reduced pressure, and 1 N aqueous sodium hydroxide and water
  4. additionwere added to the resulting mixture, which
  5. filtrationwas filtered
  6. customto isolate a solid
  7. washThe solid was washed with diethyl ether
  8. customAdditional solid precipitated from the aqueous filtrate
  9. customwas isolated by filtration

Sources & evidence

ORD record
ord-58cf268f85ea49f3bc55e21ff6049c3f
Source dataset
uspto-grants-2011_03
Patent number
US07915281B2

Reaction notes

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