Formaldehyde → N-{(1S,2S)-1-[(2,4-Dimethyl-benzylamino)-methyl]-2-hydroxy-pentyl}-N'-(3-methylamino-5-trifluoromethyl-phenyl)-malonamide

HRID 1766834Notes

Reaction equation

HRID 1766834 reaction equation
C(OC(=O)[N:10]([CH2:20][C@H:21]([NH:27][C:28](=[O:44])[CH2:29][C:30](=[O:43])[NH:31][C:32]1[CH:37]=[C:36]([C:38]([F:41])([F:40])[F:39])[CH:35]=[C:34]([NH2:42])[CH:33]=1)[C@@H:22]([OH:26])[CH2:23][CH2:24][CH3:25])[CH2:11][C:12]1[CH:17]=[CH:16][C:15]([CH3:18])=[CH:14][C:13]=1[CH3:19])C1C=CC=CC=1.C=O.[C:48](O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl>[CH3:19][C:13]1[CH:14]=[C:15]([CH3:18])[CH:16]=[CH:17][C:12]=1[CH2:11][NH:10][CH2:20][C@H:21]([NH:27][C:28](=[O:44])[CH2:29][C:30]([NH:31][C:32]1[CH:37]=[C:36]([C:38]([F:41])([F:40])[F:39])[CH:35]=[C:34]([NH:42][CH3:48])[CH:33]=1)=[O:43])[C@@H:22]([OH:26])[CH2:23][CH2:24][CH3:25]

Participants

5

Reactant 3

HCID 712FormaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 68616642{(2S,3S)-2-[2-(3-amino-5-trifluoromethyl-phenylcarbamoyl)-acetylamino]-3-hydroxyhexyl}-(2,4-dimethyl-benzyl)-carbamic acid benzyl ester

Product 1

HCID 11306757N-{(1S,2S)-1-[(2,4-Dimethyl-benzylamino)-methyl]-2-hydroxy-pentyl}-N'-(3-methylamino-5-trifluoromethyl-phenyl)-malonamide

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

A solution of {(2S,3S)-2-[2-(3-amino-5-trifluoromethyl-phenylcarbamoyl)-acetylamino]-3-hydroxyhexyl}-(2,4-dimethyl-benzyl)-carbamic acid benzyl ester (83 mg, 0.13 mmol, see procedure 12c) in 1,2-dichloroethane (2 mL) was charged with formaldehyde (0.008 mL of a 37% aq. solution, 0.10 mmol), stirred for 20 min at RT, and then charged with sodium triacetoxyborohydride (69 mg, 0.33 mmol). The reaction was stirred at RT for 40 min, quenched with water, and extracted with EtOAc (2×). The organic extracts were washed with water and brine, and then dried (Na2SO4), filtered, and concentrated in vacuo. The residue was dissolved in MeOH (2 mL). This solution was charged with 5% Pd/C, Degussa style (7 mg), stirred under H2 (1 atm) for 12 h at RT, 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)+=509.3.

Workup

  1. stirringThe reaction was stirred at RT for 40 min
  2. customquenched with water
  3. extractionextracted with EtOAc (2×)
  4. washThe organic extracts were washed with water and brine
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. dissolutionThe residue was dissolved in MeOH (2 mL)
  9. additionThis solution was charged with 5% Pd/C, Degussa style (7 mg)
  10. stirringstirred under H2 (1 atm) for 12 h at RT
  11. filtrationfiltered
  12. concentrationconcentrated in vacuo
  13. customPurification of the residue by reverse-phase HPLC

Sources & evidence

ORD record
ord-cae0870e7ea9451ea2fe68e14c88a068
Source dataset
uspto-grants-2007_06
Patent number
US07230133B2

Reaction notes

Loading…