Benzylamine → HCID 22036952, compound

HRID 2217307Notes

Reaction equation

HRID 2217307 reaction equation
[N:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][C:9]=2[N:11]2[C:15]3[CH:16]=[CH:17][CH:18]=[CH:19][C:14]=3[N:13]=[C:12]2[NH:20][CH:21]2[CH2:26][CH2:25][N:24]([CH2:27][C:28](=[O:32])[CH:29]([CH3:31])[CH3:30])[CH2:23][CH2:22]2)[CH:4]=[CH:3][CH:2]=1.C1(CN)C=CC=CC=1>CO.[Pd]>[NH:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][C:9]=2[N:11]2[C:15]3[CH:16]=[CH:17][CH:18]=[CH:19][C:14]=3[N:13]=[C:12]2[NH:20][CH:21]2[CH2:26][CH2:25][N:24]([CH2:27][C:28](=[O:32])[CH:29]([CH3:30])[CH3:31])[CH2:23][CH2:22]2)[CH2:4][CH2:3][CH2:2]1

Participants

5

Reactant 2

HCID 7504BenzylamineHCID 22036963HCID 22036963, compound

Product 1

HCID 22036952HCID 22036952, compoundYield 27.1%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Procedure

A mixture of 1-[4-[[1-(8-quinolinyl)-1H-benzimidazol-2-yl]amino]-1-piperidinyl]-3-methyl-2-butanone (0.0222 mol) and benzenemethanamine (0.0666 mol) in methanol (250 ml) was hydrogenated at 40° C. under a 3 bar pressure for 24 hours with palladium on activated carbon (1.5 g) as a catalyst. After uptake of hydrogen, the catalyst was filtered through celite, washed with CH2Cl2 and CH3OH and the filtrate was evaporated. Palladium on activated carbon (1.5 g) and methanol (250 ml) were added again. Hydrogenation was continued at 40° C. under a 3 bar pressure for 24 hours. After uptake of hydrogen, the catalyst was filtered through celite, washed with CH2Cl2 and the filtrate was evaporated. The residue (22 g) was purified by column chromatography over silica gel (eluent: CH2Cl2/CH3OH/NH4OH 95/5/0.1 and 85/15/1; 20-45 μm). Three pure fractions were collected and their solvents were evaporated, yielding 2.6 g 1-[4-[[1-(1,2,3,4-tetrahydro-8-quinolinyl)-1H-benzimidazol-2-yl]amino]-1-piperidinyl]-3-methyl-2-butanone (interm. 40) (fraction 1), 2.9 g of fraction 2 and 0.7 g of fraction 3. Fraction 2 and 3 were crystallized from CH3CN. The precipitate was filtered off and dried, yielding 0.82 g (±)-N-[1-[3-methyl-2-[(phenylmethyl)amino]butyl]-4-piperidinyl]-1-(1,2,3,4-tetrahydro-8-quinolinyl)-1H-benzimidazol-2-amine; mp. 126° C. and 0.55 g of N-(4-piperidinyl)-1-(1,2,3,4-tetrahydro-8-quinolinyl)-1H-benzimidazol-2-amine; mp. 205° C. (comp. 48).

Workup

  1. filtrationAfter uptake of hydrogen, the catalyst was filtered through celite
  2. washwashed with CH2Cl2 and CH3OH
  3. customthe filtrate was evaporated
  4. additionPalladium on activated carbon (1.5 g) and methanol (250 ml) were added again
  5. filtrationAfter uptake of hydrogen, the catalyst was filtered through celite
  6. washwashed with CH2Cl2
  7. customthe filtrate was evaporated
  8. customThe residue (22 g) was purified by column chromatography over silica gel (eluent: CH2Cl2/CH3OH/NH4OH 95/5/0.1 and 85/15/1; 20-45 μm)
  9. customThree pure fractions were collected
  10. customtheir solvents were evaporated

Sources & evidence

ORD record
ord-d7df96ed6e92471fb207abd9b801d182
Source dataset
uspto-grants-2008_08
Patent number
US07407969B2

Reaction notes

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