Hydrochloric Acid → 6-Chloro-2-(4-chloro-2-fluoro-3-methoxyphenyl)-7-methyl-7H-purine

HRID 1969364Notes

Reaction equation

HRID 1969364 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:16]=[C:15]3[C:11]([N:12]([CH3:17])[CH:13]=[N:14]3)=[C:10](OC)[N:9]=2)=[C:4]([F:20])[C:3]=1[O:21][CH3:22].Cl.[OH-].[Na+].CN(C=O)C.S(Cl)([Cl:33])=O>O.C(OCC)(=O)C>[Cl:33][C:10]1[N:9]=[C:8]([C:5]2[CH:6]=[CH:7][C:2]([Cl:1])=[C:3]([O:21][CH3:22])[C:4]=2[F:20])[N:16]=[C:15]2[C:11]=1[N:12]([CH3:17])[CH:13]=[N:14]2

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 6228DimethylformamideHCID 14798Sodium Hydroxide2×HCID 24386Thionyl ChlorideHCID 591269312-(4-Chloro-2-fluoro-3-methoxyphenyl)-6-methoxy-7-methyl-7H-purine

Product 1

HCID 591269396-Chloro-2-(4-chloro-2-fluoro-3-methoxyphenyl)-7-methyl-7H-purineYield 49.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Procedure

2-(4-Chloro-2-fluoro-3-methoxyphenyl)-6-methoxy-7-methyl-7H-purine (1.0 g, 3.1 mmol) was combined with 10 mL 6M HCl and heated at reflux for 2 h. After cooling, the mixture was diluted with 15 mL water and the pH was adjusted to 2 by addition of 2M aqueous sodium hydroxide. The precipitated material was collected by filtration, washed with water and dried under vacuum at 80° C. A 500 mg sample of the crude intermediate was slurried in chloroform (10 mL), treated with DMF (0.62 mL, 580 mg, 8.0 mmol) and then with thionyl chloride (0.58 mL, 950 mg, 8.0 mmol). The mixture was heated at reflux for 3 h, cooled and poured into 20 mL of ice-water. The pH was adjusted to 10 by addition of 1M sodium hydroxide. The precipitated product was taken up in ethyl acetate, washed twice with water, once with brine, dried and evaporated to give the title compound (500 mg, 49% yield over two steps): mp 184-186° C.: 1H NMR (DMSO-d6) δ 8.8 (s, 1H), 7.8 (dd, 1H), 7.46 (dd, 1H), 4.11 (s, 3H), 3.96 (s, 3H).

Workup

  1. temperatureheated
  2. temperatureat reflux for 2 h
  3. temperatureAfter cooling
  4. filtrationThe precipitated material was collected by filtration
  5. washwashed with water
  6. customdried under vacuum at 80° C
  7. temperatureThe mixture was heated
  8. temperatureat reflux for 3 h
  9. temperaturecooled
  10. washwashed twice with water, once with brine
  11. customdried
  12. customevaporated

Sources & evidence

ORD record
ord-f99092f317874a92b7b83a0ed4209770
Source dataset
uspto-grants-2013_04
Patent number
US08426591B2

Reaction notes

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