HCID 70124084, compound → HCID 20703633, compound

HRID 429290Notes

Reaction equation

HRID 429290 reaction equation
C(O[C:9]([N:11]1[CH2:16][CH2:15][N:14](C(OC(C)(C)C)=O)[CH2:13][CH:12]1[CH:24]([NH:26][C:27]1[N:32]=[C:31]([N:33]2[C:37]3[CH:38]=[CH:39][CH:40]=[CH:41][C:36]=3[N:35]=[CH:34]2)[CH:30]=[CH:29][N:28]=1)[CH3:25])=O)C1C=CC=CC=1>CO.[OH-].[OH-].[Pd+2]>[CH3:9][N:11]1[CH2:16][CH2:15][NH:14][CH2:13][CH:12]1[CH:24]([NH:26][C:27]1[N:32]=[C:31]([N:33]2[C:37]3[CH:38]=[CH:39][CH:40]=[CH:41][C:36]=3[N:35]=[CH:34]2)[CH:30]=[CH:29][N:28]=1)[CH3:25]

Participants

4

Reactant 1

HCID 70124084HCID 70124084, compound

Product 1

HCID 20703633HCID 20703633, compoundYield 51.8%

Reagents, catalysts & solvents 2

HCID 9942167Palladium hydroxideCatalystHCID 887MethanolSolvent

Procedure

A solution of 2-[1-(1-(benzyloxycarbonyl)-4-(tert-butyloxycarbonyl)-piperazin-2-yl)-ethylamino]-4-(benzimidazol-1-yl)-pyrimidine (EXAMPLE 14, Step E; 30 mg) in 3 mL of MeOH was stirred over Pd(OH)2/C (30 mg) under an H2 atmosphere (balloon) for 4 h, then filtered through Celite®, washing liberally with MeOH, and concentrated. The residue was dissolved in 1 mL of MeOH and NaBH3CN (6.8 mg) and 37% aqueous formaldehyde (26 μL) were added and the mixture was stirred for 5 h at room temperature, then diluted with 5 mL of EtOAc and poured into 10 mL of water. The phases were separated and the aqueous phase was extracted with 2×5 mL of EtOAc. The aqueous phase was basified (pH>10) by addition of 5N NaOH, then extracted with 5×5 mL of EtOAc. The combined organic extracts were washed with 5 mL of brine, dried over Na2SO4, and concentrated. The residue (16 mg) was dissolved in 1 mL of CH2Cl2 and 0.5 mL of trifluoroacetic acid was added. The mixture was stirred for 1 h at room temperature, then poured into 10 mL of water and extracted with 2×5 mL of CH2Cl2. The aqueous phase was basified (pH>10) by addition of 5N NaOH, then extracted with 4×5 mL of EtOAc. The combined organic extracts were washed with 5 mL of brine, dried over Na2SO4, and concentrated. The residue was purified by preparative thin-layer chromatography, eluting with 9:1 CH2Cl2—2M NH3 in MeOH to provide 9.4 mg of the title compound. Mass spectrum (ESI) 338.3 (M+1).

Workup

  1. filtrationfiltered through Celite®
  2. washwashing liberally with MeOH
  3. concentrationconcentrated
  4. dissolutionThe residue was dissolved in 1 mL of MeOH
  5. additionNaBH3CN (6.8 mg) and 37% aqueous formaldehyde (26 μL) were added
  6. additiondiluted with 5 mL of EtOAc
  7. additionpoured into 10 mL of water
  8. customThe phases were separated
  9. extractionthe aqueous phase was extracted with 2×5 mL of EtOAc
  10. additionby addition of 5N NaOH
  11. extractionextracted with 5×5 mL of EtOAc
  12. washThe combined organic extracts were washed with 5 mL of brine
  13. dry with materialdried over Na2SO4
  14. concentrationconcentrated
  15. dissolutionThe residue (16 mg) was dissolved in 1 mL of CH2Cl2
  16. addition0.5 mL of trifluoroacetic acid was added
  17. stirringThe mixture was stirred for 1 h at room temperature
  18. additionpoured into 10 mL of water
  19. extractionextracted with 2×5 mL of CH2Cl2
  20. additionby addition of 5N NaOH
  21. extractionextracted with 4×5 mL of EtOAc
  22. washThe combined organic extracts were washed with 5 mL of brine
  23. dry with materialdried over Na2SO4
  24. concentrationconcentrated
  25. customThe residue was purified by preparative thin-layer chromatography
  26. washeluting with 9:1 CH2Cl2—2M NH3 in MeOH

Sources & evidence

ORD record
ord-97161b6219f449fd918858282669d8d6
Source dataset
uspto-grants-2001_11
Patent number
US06316444B1

Reaction notes

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