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Bromine → 8-Bromo-2-butoxy-9-(6-chloro-3-pyridylmethyl)adenine

HRID 1371462
Notes
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Reaction equation

HRID 1371462 reaction equation
[Br:1]Br.C([O-])(=O)C.[Na+].[CH2:8]([O:12][C:13]1[N:21]=[C:20]2[C:16]([N:17]=[CH:18][N:19]2[CH2:22][C:23]2[CH:24]=[N:25][C:26]([Cl:29])=[CH:27][CH:28]=2)=[C:15]([NH2:30])[N:14]=1)[CH2:9][CH2:10][CH3:11]>C(O)(=O)C>[Br:1][C:18]1[N:19]([CH2:22][C:23]2[CH:24]=[N:25][C:26]([Cl:29])=[CH:27][CH:28]=2)[C:20]2[C:16]([N:17]=1)=[C:15]([NH2:30])[N:14]=[C:13]([O:12][CH2:8][CH2:9][CH2:10][CH3:11])[N:21]=2
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

5

Reactant 3

HCID 24408BromineHCID 517045Sodium AcetateHCID 229289322-Butoxy-9-(6-chloro-3-pyridylmethyl)adenine

Product 1

HCID 229289138-Bromo-2-butoxy-9-(6-chloro-3-pyridylmethyl)adenineYield 62.1%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

Potassium carbonate (2.85 g, 20.6 mmol) and 2-chloro-5-chloromethylpyridine (3.33 g, 20.6 mmol) were added to the DMF solution (125 ml) of 2-butoxyadenine (2.60 g, 12.5 mmol) obtained in Reference Example 1. The resultant was stirred while heating at 80° C. for 2.5 hours. The reaction solution was concentrated under reduced pressure, water (100 ml) was added thereto, and the resultant was neutralized with 1N hydrochloric acid. The precipitated solid was collected by filtration. The resulting solid was dissolved in methylene chloride (100 ml), hexane (150 ml) was added under ice cooling, and the precipitated crystal was collected by filtration. Thus, 2-butoxy-9-(6-chloro-3-pyridylmethyl)adenine was obtained (yield: 3.12 g). Bromine (1.92 ml, 37.5 mmol) was added to an acetic acid suspension (186 ml) comprising sodium acetate (3.05 g, 37.2 mmol) and 2-butoxy-9-(6-chloro-3-pyridylmethyl)adenine (3.1 g, 9.31 mmol) at room temperature, and the resultant was allowed to react for 4 hours. The reaction solution was removed by distillation under reduced pressure, water (200 ml) was added to the residue, and the resultant was neutralized with 5N sodium hydroxide under ice cooling. The precipitated crystal was collected by filtration, and crude crystal was recrystalized with the aid of methanol. The resultant was dried under reduced pressure at 40° C. for 15 hours. Thus, 2.38 g of the title compound was obtained as a white powdery crystal (yield: 62%).

Workup

  1. customat room temperature
  2. customto react for 4 hours
  3. customThe reaction solution was removed by distillation under reduced pressure, water (200 ml)
  4. additionwas added to the residue
  5. filtrationThe precipitated crystal was collected by filtration
  6. customcrude crystal was recrystalized with the aid of methanol
  7. customThe resultant was dried under reduced pressure at 40° C. for 15 hours

Sources & evidence

ORD record
ord-94f04619dd5d470baf0f83076efb6abf
Source dataset
uspto-grants-2007_01
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US07157465B2

Reaction notes

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On this pageParticipantsProcedureWorkupSources & evidenceReaction notes