Hydrochloric Acid → HCID 22326811, compound

HRID 495488Notes

Reaction equation

HRID 495488 reaction equation
[H-].[Na+].[CH3:3][C:4]1[CH:9]=[CH:8][CH:7]=[C:6]([CH3:10])[C:5]=1[NH:11][C:12]1[NH:16][C:15]2[CH:17]=[CH:18][CH:19]=[CH:20][C:14]=2[N:13]=1.[Cl:21][C:22]1[N:27]=[C:26](Cl)[CH:25]=[CH:24][N:23]=1.Cl.CCOCC>C1COCC1.C(Cl)Cl.C([O-])(O)=O.[Na+].CC#N>[Cl:21][C:22]1[N:27]=[C:26]([N:11]([C:5]2[C:6]([CH3:10])=[CH:7][CH:8]=[CH:9][C:4]=2[CH3:3])[C:12]2[NH:13][C:14]3[CH:20]=[CH:19][CH:18]=[CH:17][C:15]=3[N:16]=2)[CH:25]=[CH:24][N:23]=1

Participants

10

Reactant 5

HCID 313Hydrochloric Acid2×HCID 3283Diethyl EtherHCID 24758Sodium hydrideHCID 775312,4-DichloropyrimidineHCID 17750887N-(2,6-Dimethylphenyl)-1H-benzimidazol-2-amine

Product 1

HCID 22326811HCID 22326811, compound

Reagents, catalysts & solvents 4

HCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolvent2×HCID 8028TetrahydrofuranSolvent2×HCID 516892Sodium BicarbonateSolvent

Conditions

Temperature
0 °C

Procedure

A 3-neck round bottom flask was charged with NaH (60% dispersion in mineral oil, 0.41 g, 10.1 mmol, 1.2 eq.) under N2. The mineral oil was removed by stirring in n-heptane (3×10 mL) and decanting the supernatant liquid. The NaH was suspended in anhydrous THF (20 mL) and cooled to 0° C. A solution of 2-(2,6-dimethylphenylamino)-1H-benzimidazole (2.0 g, 8.4 mmol) in anhydrous THF (15 mL) was added slowly and the reaction was stirred at 0° C. for 0.5 h. A solution of 2,4-dichloropyrimidine (1.89 g, 12.7 mmol, 1.5 eq.) in anhydrous THF (15 mL) was added and the reaction was stirred at 0° C. for 0.5 h under N2, then warmed to RT and stirred for 18 h. The reaction was diluted with CH2Cl2 and sat. aq. NaHCO3. The organic layer was separated, dried (Na2SO4) and concentrated in vacuo. The residue was taken up into IPA and triturated with 1M HCl in Et2O (16 mmol). The resulting precipitate was separated by filtration and rinsed with n-heptane and n-heptane/EtOAc (1:1) to yield off-white crystals of a mixture of regioisomers as the HCl salts. The salts were suspended in hot CH3CN and filtered. The solids, a mixture of regioisomers, was taken up into CH2Cl2 and free-based with sat. aq. NaHCO3. The organic layer was dried (Na2SO4) and concentrated in vacuo to afford a fluffy white solid. The solids were dissolved in CH2Cl2, adsorbed onto silica and purified by column chromatography (silica; n-heptane:EtOAc; 4:1). The product fractions were combined and the solvent removed in vacuo to afford 2-(N-(2-chloropyrimid-4-yl)-2,6-dimethylphenylamino)-1H-benzimidazole as a white solid. MS m/z=350 (M+H). Calc'd for C19H40N8O3=349.

Workup

  1. customThe mineral oil was removed
  2. customdecanting the supernatant liquid
  3. stirringthe reaction was stirred at 0° C. for 0.5 h
  4. stirringthe reaction was stirred at 0° C. for 0.5 h under N2
  5. temperaturewarmed to RT
  6. stirringstirred for 18 h
  7. customThe organic layer was separated
  8. dry with materialdried (Na2SO4)
  9. concentrationconcentrated in vacuo
  10. customThe resulting precipitate was separated by filtration
  11. washrinsed with n-heptane and n-heptane/EtOAc (1:1)
  12. customto yield off-white
  13. filtrationfiltered
  14. additionThe solids, a mixture of regioisomers
  15. dry with materialThe organic layer was dried (Na2SO4)
  16. concentrationconcentrated in vacuo
  17. customto afford a fluffy white solid
  18. custompurified by column chromatography (silica; n-heptane:EtOAc; 4:1)
  19. customthe solvent removed in vacuo

Sources & evidence

ORD record
ord-e89aec00d924452fbf33ad8a5e1ff7d0
Source dataset
uspto-grants-2005_09
Patent number
US06939874B2

Reaction notes

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