Hydrochloric Acid → HCID 58967529, compound

HRID 909363Notes

Reaction equation

HRID 909363 reaction equation
[NH2:1][C:2]1[C:11]2[N:12]=[C:13]([CH2:19][O:20]CC)[N:14]([CH2:15][CH:16]([CH3:18])[CH3:17])[C:10]=2[C:9]2[N:8]=[CH:7][C:6]([N:23]3[CH2:27][CH2:26][CH2:25][C:24]3=[O:28])=[CH:5][C:4]=2[N:3]=1.B(Br)(Br)Br.Cl.[OH-].[Na+]>ClCCl>[NH2:1][C:2]1[C:11]2[N:12]=[C:13]([CH2:19][OH:20])[N:14]([CH2:15][CH:16]([CH3:18])[CH3:17])[C:10]=2[C:9]2[N:8]=[CH:7][C:6]([N:23]3[CH2:27][CH2:26][CH2:25][C:24]3=[O:28])=[CH:5][C:4]=2[N:3]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 25134Boron tribromideHCID 58967522HCID 58967522, compound

Product 1

HCID 58967529HCID 58967529, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

1-[4-Amino-2-(ethoxymethyl)-1-(2-methylpropyl)-1H-imidazo[4,5-c]-1,5-naphthyridin-7-yl]pyrrolidin-2-one (0.150 g, 0.39 mmol) from Example 13 was dissolved in dichloromethane (5 mL) and cooled with an ice bath. Boron tribromide (0.5 mL of a 1.0 M solution in dichloromethane) was added dropwise over 1 minute. The resulting slurry was stirred for 16 hours. The reaction mixture was acidified with 6 N hydrochloric acid (3 mL). The mixture was stirred until all of the solids dissolved. The biphasic mixture was made basic with 50% aqueous sodium hydroxide (˜6 mL). The layers were separated and the aqueous fraction was extracted with dichloromethane, followed by extraction with a 10% methanol in dichloromethane solution. The organic fractions were combined and concentrated under vacuum. The residue was purified by HPFC eluting with a linear gradient of 2-30% CMA in chloroform. Recrystallization from acetonitrile afforded 1-[4-amino-2-(hydroxymethyl)-1-(2-methylpropyl)-1H-imidazo[4,5-c][1,5]naphthyridin-7-yl]pyrrolidin-2-one as 0.034 g of a white powder, m.p. 233-235° C.

Workup

  1. temperaturecooled with an ice bath
  2. stirringThe mixture was stirred until all of the solids
  3. dissolutiondissolved
  4. customThe layers were separated
  5. extractionthe aqueous fraction was extracted with dichloromethane
  6. extractionfollowed by extraction with a 10% methanol in dichloromethane solution
  7. concentrationconcentrated under vacuum
  8. customThe residue was purified by HPFC
  9. washeluting with a linear gradient of 2-30% CMA in chloroform
  10. customRecrystallization from acetonitrile

Sources & evidence

ORD record
ord-d70efb58b5764c7ba7df100c8e28f6e5
Source dataset
uspto-grants-2011_09
Patent number
US08017779B2

Reaction notes

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