Chloroform → 2-Anilino-6-chloro-9-(2,3-epoxypropyl)purine

HRID 263939Notes

Reaction equation

HRID 263939 reaction equation
[H-].[Na+].[NH:3]([C:10]1[N:18]=[C:17]2[C:13]([NH:14][CH:15]=[N:16]2)=[C:12]([Cl:19])[N:11]=1)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.[CH2:20]([CH:22]1[O:24][CH2:23]1)Br.C(Cl)(Cl)Cl>C(#N)C>[NH:3]([C:10]1[N:18]=[C:17]2[C:13]([N:14]=[CH:15][N:16]2[CH2:20][CH:22]2[O:24][CH2:23]2)=[C:12]([Cl:19])[N:11]=1)[C:4]1[CH:5]=[CH:6][CH:7]=[CH:8][CH:9]=1

Participants

6

Reactant 4

HCID 6212ChloroformHCID 18430EpibromohydrinHCID 24758Sodium hydrideHCID 52718829H-Purin-2-amine, 6-chloro-N-phenyl-

Product 1

HCID 104249662-Anilino-6-chloro-9-(2,3-epoxypropyl)purineYield 34.6%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

Sodium hydride (161 mg, 4 mmol; 60% suspension in mineral oil) was added to a suspension of 2-anilino-6-chloropurine (1 g, 4 mmol; Focher et al. (1988) J. Med. Chem. 31:1496-1500) in anhydrous acetonitrile (240 ml) at room temperature. After stirring for 1 hr epibromohydrin (0.35 ml, 4 mmol) was added, and the suspension was stirred for 48 hr. An equal volume of chloroform was added, and, after filtration through Celite, the filtrate was evaporated to dryness. The residue was chromatographed on silica gel, and the major product was eluted with chloroform to give 417 mg (34% yield) of 2-anilino-6-chloro-9-(2,3-epoxypropyl)purine. 1H NMR δ9.97 (s, 2-NH), 8.24 (s, 8-H), 7.40 (m, C6H5), 4.38 (m, 1'-CH2), 3.45 (m, 2'-CH), 2.72 (m, 3'-CH2). Further elution gave 46 mg (3.8% yield) of the minor 7-isomer.

Workup

  1. additionwas added
  2. filtrationafter filtration through Celite
  3. customthe filtrate was evaporated to dryness
  4. customThe residue was chromatographed on silica gel
  5. washthe major product was eluted with chloroform

Sources & evidence

ORD record
ord-b1d5203ab8be4f64b0f7e7d1cc22f826
Source dataset
uspto-grants-1997_07
Patent number
US05646155

Reaction notes

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