2,4-Dimethylbenzaldehyde → N-{(1S,2S)-1-[(2,4-Dimethyl-benzylamino)-methyl]-2-hydroxy-pentyl}-2-(4-trifluoromethyl-1H-benzoimidazol-2-yl)-acetamide

HRID 1766848Notes

Reaction equation

HRID 1766848 reaction equation
C(O[C:9](=O)[NH:10][CH2:11][C@H:12]([NH:18][C:19](=[O:34])[CH2:20][C:21]1[NH:25][C:24]2[CH:26]=[CH:27][CH:28]=[C:29]([C:30]([F:33])([F:32])[F:31])[C:23]=2[N:22]=1)[C@@H:13]([OH:17])[C:14]#[C:15][CH3:16])C1C=CC=CC=1.[CH3:36][C:37]1[CH:44]=[C:43]([CH3:45])[CH:42]=[CH:41][C:38]=1C=O.C([BH3-])#N.[Na+]>CO.[Pd]>[CH3:36][C:37]1[CH:44]=[C:43]([CH3:45])[CH:42]=[CH:41][C:38]=1[CH2:9][NH:10][CH2:11][C@H:12]([NH:18][C:19](=[O:34])[CH2:20][C:21]1[NH:25][C:24]2[CH:26]=[CH:27][CH:28]=[C:29]([C:30]([F:31])([F:33])[F:32])[C:23]=2[N:22]=1)[C@@H:13]([OH:17])[CH2:14][CH2:15][CH3:16]

Participants

6

Reactant 3

HCID 618142,4-DimethylbenzaldehydeHCID 5003444Sodium cyanoborohydrideHCID 69289705{(2S,3S)-3-hydroxy-2-[2-(4-trifluoromethyl-1H-benzoimidazol-2-yl)-acetylamino]-hex-4-ynyl}-carbamic acid benzyl ester

Product 1

HCID 11155781N-{(1S,2S)-1-[(2,4-Dimethyl-benzylamino)-methyl]-2-hydroxy-pentyl}-2-(4-trifluoromethyl-1H-benzoimidazol-2-yl)-acetamide

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Procedure

A solution of {(2S,3S)-3-hydroxy-2-[2-(4-trifluoromethyl-1H-benzoimidazol-2-yl)-acetylamino]-hex-4-ynyl}-carbamic acid benzyl ester (87 mg, 0.18 mmol) in MeOH (3 mL) was charged with 5% Pd/C, Degussa style (17 mg), stirred under H2 (1 atm) for 12 h at RT, filtered, and concentrated in vacuo. The residue was dissolved in MeOH (3 mL). The resultant solution was charged sequentially with 2,4-dimethylbenzaldehyde (0.024 mL, 0.16 mmol) and sodium cyanoborohydride (12 mg, 0.2 mmol), stirred for 12 h at RT, quenched with sat. NaHCO3, and extracted twice with EtOAc. The organic extracts were combined, washed with brine, dried (Na2SO4), filtered, and concentrated in vacuo. Purification of the residue by reverse-phase HPLC provided the title compound as a white powder after lyopholization. MS found: (M+H)+=477.4.

Workup

  1. filtrationfiltered
  2. concentrationconcentrated in vacuo
  3. dissolutionThe residue was dissolved in MeOH (3 mL)
  4. stirringstirred for 12 h at RT
  5. customquenched with sat. NaHCO3
  6. extractionextracted twice with EtOAc
  7. washwashed with brine
  8. dry with materialdried (Na2SO4)
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customPurification of the residue by reverse-phase HPLC

Sources & evidence

ORD record
ord-212da0099e214b1db3003a9abe879cb7
Source dataset
uspto-grants-2007_06
Patent number
US07230133B2

Reaction notes

Loading…