HCID 18332609, compound → HCID 18332638, compound

HRID 2268947Notes

Reaction equation

HRID 2268947 reaction equation
C(OC([N:11]1[CH2:16][CH2:15][CH2:14][CH:13]([N:17]([CH3:33])[C:18]2[N:23]=[C:22]([N:24]3[C:28]4[CH:29]=[CH:30][CH:31]=[CH:32][C:27]=4[N:26]=[CH:25]3)[CH:21]=[CH:20][N:19]=2)[CH2:12]1)=O)C1C=CC=CC=1>C1COCC1.[Pd]>[NH3:11].[NH:11]1[CH2:16][CH2:15][CH2:14][CH:13]([N:17]([CH3:33])[C:18]2[N:23]=[C:22]([N:24]3[C:28]4[CH:29]=[CH:30][CH:31]=[CH:32][C:27]=4[N:26]=[CH:25]3)[CH:21]=[CH:20][N:19]=2)[CH2:12]1

Participants

5

Reactant 1

HCID 18332609HCID 18332609, compound

Product 2

HCID 222AmmoniaHCID 18332638HCID 18332638, compoundYield 152.7%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 2-[(1-benzyloxycarbonyl-piperidin-3-yl)-methylamino]-4-[benzimidazol-1-yl]pyrimidine (100 mg, 0.226 mmol, 1 eq) in THF (5 mL) ws added 10% Pd on carbon (24 mg). The flask was purged with hydrogen and the mixture was stirred under a balloon of hydrogen. After 1 h, no reaction was observed by thin layer chromatography analysis. Added 12 mg of Pd(OH)2 and let stir overnight under hydrogen. Still very little reaction by thin layer chromatography analysis. Filtered off catalyst and washed with THF and MeOH. Concentrated under reduced pressure. Dissolved the residue in MeOH (5 mL) and added Pd(OH)2 (24 mg). Purged flask with H2 and stirred under a balloon of H2 for several hours. Purged the vessel with nitrogen and filtered off and washed the catalyst with methanol. Concentrated the mixture under reduced pressure and purified by silica gel chromatography (eluted with 3.5% MeOH/CH2Cl2 then 7% (2N NH3 in MeOH)/CH2Cl2) to give 53.2 mg of the title compound. 1H NMR (500 MHz, CDCl3): δ 1.2-1.3 (1H, m), 1.4-1.5 (1H, m), 1.55-1.95 (3H, m), 2.61 (1H, dd, J=10 Hz, J=11.5 Hz), 2.62 (1H, dd, J=2.5 Hz, J=12 Hz), 3.03 (1H, d, J=12 Hz), 3.19 (1H, d, J=11.5 Hz), 3.4-3.45(2H, m), 5.5 (1H br s), 6.8 (1H, d, 5.5 Hz), 7.40-7.45 (2H, m), 7.87 (1H, d, J=8.5 Hz), 8.20 (1H br d), 8.39 (1H, br s), 8.64 (1H, s). Mass spectrum (ESI) 309.1 (M+1).

Workup

  1. customThe flask was purged with hydrogen
  2. additionAdded 12 mg of Pd(OH)2
  3. stirringlet stir overnight under hydrogen
  4. customStill very little reaction by thin layer chromatography analysis
  5. filtrationFiltered off catalyst
  6. washwashed with THF and MeOH
  7. concentrationConcentrated under reduced pressure
  8. dissolutionDissolved the residue in MeOH (5 mL)
  9. additionadded Pd(OH)2 (24 mg)
  10. customPurged flask with H2
  11. stirringstirred under a balloon of H2 for several hours
  12. customPurged the vessel with nitrogen
  13. filtrationfiltered off
  14. washwashed the catalyst with methanol
  15. concentrationConcentrated the mixture under reduced pressure
  16. custompurified by silica gel chromatography (
  17. washeluted with 3.5% MeOH/CH2Cl2

Sources & evidence

ORD record
ord-72f120c373e3454da9f7596f137f91e3
Source dataset
uspto-grants-2001_12
Patent number
US06329380B1

Reaction notes

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