4-Toluenesulfonyl chloride → 1-[4-amino-7-bromo-2-(ethoxymethyl)-1H-imidazo[4,5-c][1,5]naphthyridin-1-yl]-2-methylpropan-2-ol

HRID 909362Notes

Reaction equation

HRID 909362 reaction equation
C1C=C(Cl)C=C(C(OO)=O)C=1.[Br:12][C:13]1[CH:14]=[N:15][C:16]2[C:17]3[N:25]([CH2:26][C:27]([CH3:30])([OH:29])[CH3:28])[C:24]([CH2:31][O:32][CH2:33][CH3:34])=[N:23][C:18]=3[CH:19]=[N:20][C:21]=2[CH:22]=1.[OH-].[NH4+:36].C1(C)C=CC(S(Cl)(=O)=O)=CC=1>C(Cl)(Cl)Cl>[NH2:36][C:19]1[C:18]2[N:23]=[C:24]([CH2:31][O:32][CH2:33][CH3:34])[N:25]([CH2:26][C:27]([CH3:28])([OH:29])[CH3:30])[C:17]=2[C:16]2[N:15]=[CH:14][C:13]([Br:12])=[CH:22][C:21]=2[N:20]=1

Participants

6

Reactant 4

HCID 73974-Toluenesulfonyl chloride3×HCID 14923Ammonium Hydroxide2×HCID 70297m-Chloroperbenzoic acidHCID 670524691-[7-bromo-2-(ethoxymethyl)-1H-imidazo[4,5-c][1,5]naphthyridin-1-yl]-2-methylpropan-2-ol

Product 1

HCID 589706811-[4-amino-7-bromo-2-(ethoxymethyl)-1H-imidazo[4,5-c][1,5]naphthyridin-1-yl]-2-methylpropan-2-ol

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Procedure

mCPBA (35.5 g of 77% purity, 158 mmol) was added to a stirred solution of 1-[7-bromo-2-(ethoxymethyl)-1H-imidazo[4,5-c][1,5]naphthyridin-1-yl]-2-methylpropan-2-ol (15 g, 0.040 mol) in chloroform (400 mL), and the reaction was stirred at room temperature for 2.5 hours. Concentrated ammonium hydroxide (200 mL) was added, and then p-toluenesulfonyl chloride (18.9 g, 98.9 mmol) was added over a period of five minutes. The reaction mixture was stirred at room temperature for 2.5 hours, and an analysis by LC/MS indicated the presence of starting material. Additional p-toluenesulfonyl chloride (11 g) was added, and the reaction mixture was stirred at room temperature for one hour. An analysis by LC/MS indicated the reaction was still incomplete. Additional ammonium hydroxide (100 mL) and p-toluenesulfonyl chloride (10 g) were added, and the mixture was stirred for 30 minutes at room temperature. The aqueous layer was separated and extracted with dichloromethane (2×300 mL). The combined organic fractions were dried over magnesium sulfate, filtered, and concentrated under reduced pressure. The residue (41.4 g) was purified by chromatography using a Biotage Horizon™ High-Performance Flash Chromatography instrument (65I cartridge, eluting with ethyl acetate:methanol in a gradient from 97:3 to 85:15) to provide 5.96 g of 1-[4-amino-7-bromo-2-(ethoxymethyl)-1H-imidazo[4,5-c][1,5]naphthyridin-1-yl]-2-methylpropan-2-ol as a yellow solid.

Workup

  1. stirringThe reaction mixture was stirred at room temperature for 2.5 hours
  2. stirringthe reaction mixture was stirred at room temperature for one hour
  3. stirringthe mixture was stirred for 30 minutes at room temperature
  4. customThe aqueous layer was separated
  5. extractionextracted with dichloromethane (2×300 mL)
  6. dry with materialThe combined organic fractions were dried over magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe residue (41.4 g) was purified by chromatography
  10. washeluting with ethyl acetate

Sources & evidence

ORD record
ord-64a9cb564c21493aa4d4e87d6260e335
Source dataset
uspto-grants-2011_09
Patent number
US08017779B2

Reaction notes

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