2-Methoxyethanol → 2-(3-Chloroanilino)-4-[1-(2-methoxyethyl)imidazol-5-yl]pyrimidine hydrochloride

HRID 1064305Notes

Reaction equation

HRID 1064305 reaction equation
FC(S(OS(C(F)(F)F)(=O)=O)(=O)=O)(F)F.[CH3:16][O:17][CH2:18][CH2:19]O.C(N(C(C)C)CC)(C)C.[Cl:30][C:31]1[CH:32]=[C:33]([CH:65]=[CH:66][CH:67]=1)[NH:34][C:35]1[N:40]=[C:39]([C:41]2[N:42]=[CH:43][N:44](C(C3C=CC=CC=3)(C3C=CC=CC=3)C3C=CC=CC=3)[CH:45]=2)[CH:38]=[CH:37][N:36]=1>C(Cl)Cl>[ClH:30].[Cl:30][C:31]1[CH:32]=[C:33]([CH:65]=[CH:66][CH:67]=1)[NH:34][C:35]1[N:40]=[C:39]([C:41]2[N:42]([CH2:19][CH2:18][O:17][CH3:16])[CH:43]=[N:44][CH:45]=2)[CH:38]=[CH:37][N:36]=1

Participants

6

Reactant 4

HCID 80192-MethoxyethanolHCID 67749Trifluoromethanesulfonic anhydrideHCID 81531DiisopropylethylamineHCID 222735042-(3-Chloroanilino)-4-(1-triphenylmethylimidazol-4-yl)pyrimidine

Product 1

HCID 222734762-(3-Chloroanilino)-4-[1-(2-methoxyethyl)imidazol-5-yl]pyrimidine hydrochlorideYield 69%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

Trifluoromethylsulphonic anhydride (0.16 ml, 0.93 mmol) was added to a solution of 2-methoxyethanol (73.7 ml, 0.88 mmol) and diisopropylethylamine (0.20 ml, 1.17 mmol) in DCM (1 ml) at −20° C. and the solution stirred for 30 minutes. This mixture was then added to a solution of 2-(3-chloroanilino)-4-(1-triphenylmethylimidazol-4-yl)pyrimidine Method 2; 300 mg, 0.58 mmol) in DCM (5 ml) at −20° C. and the reaction mixture allowed to warm and stirred for 2 hours at ambient temperature. The mixture was extracted between EtOAc and saturated aqueous sodium hydrogen carbonate solution. The organic phase was separated, dried and the volatiles removed by evaporation. The residue was purified by column chromatography, eluting with DCM and 7M methanolic ammonia solution (99.5:0.5 increasing in polarity to 96:4). The purified product was dissolved in either and treated with ethereal hydrogen chloride. The precipitate was collected by filtration washed with ether and dried to give the title compound 132 mg, (69%). NMR: 3.17 (s, 3H), 3.63 (t, 2H), 4.96 (t, 2H), 5.86 (br s, 1H), 7.04 (d, 1H), 7.28-7.44 (m, 2H), 7.60 (d, 1H), 7.88 (s, 1H), 8.56 (s, 1H), 8.64 (d, 1H), 9.28 (s, 1H), 10.0 (s, 1H); m/z: 330.

Workup

  1. customat −20° C.
  2. temperatureto warm
  3. stirringstirred for 2 hours at ambient temperature
  4. extractionThe mixture was extracted between EtOAc and saturated aqueous sodium hydrogen carbonate solution
  5. customThe organic phase was separated
  6. customdried
  7. customthe volatiles removed by evaporation
  8. customThe residue was purified by column chromatography
  9. washeluting with DCM and 7M methanolic ammonia solution (99.5:0.5 increasing in polarity to 96:4)
  10. dissolutionThe purified product was dissolved in either and
  11. additiontreated with ethereal hydrogen chloride
  12. filtrationThe precipitate was collected by filtration
  13. washwashed with ether
  14. customdried

Sources & evidence

ORD record
ord-30caae6076e9438c9aab0462c90c3a8c
Source dataset
uspto-grants-2005_11
Patent number
US06969714B2

Reaction notes

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