Acetone → HCID 69284549, compound

HRID 2225280Notes

Reaction equation

HRID 2225280 reaction equation
[NH2:1][C@@H:2]1[CH2:7][CH2:6][C@H:5]([NH:8][C:9](=[O:24])[CH2:10][NH:11][C:12](=[O:23])[C:13]2[CH:18]=[CH:17][CH:16]=[C:15]([C:19]([F:22])([F:21])[F:20])[CH:14]=2)[C@H:4]([C@@H:25]([OH:29])[CH:26]([CH3:28])[CH3:27])[CH2:3]1.[CH3:30][C:31]([CH3:33])=O.[C:34]([BH3-])#N.[Na+].C=O>C(Cl)Cl>[OH:29][C@H:25]([C@@H:4]1[CH2:3][C@H:2]([N:1]([CH:31]([CH3:33])[CH3:30])[CH3:34])[CH2:7][CH2:6][C@@H:5]1[NH:8][C:9](=[O:24])[CH2:10][NH:11][C:12](=[O:23])[C:13]1[CH:18]=[CH:17][CH:16]=[C:15]([C:19]([F:22])([F:21])[F:20])[CH:14]=1)[CH:26]([CH3:27])[CH3:28]

Participants

6

Reactant 4

HCID 180AcetoneHCID 712FormaldehydeHCID 5003444Sodium cyanoborohydride2×HCID 69286611HCID 69286611, compound

Product 1

HCID 69284549HCID 69284549, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

The entirety of N-(2-((1S,2R,4R)-4-amino-2-((S)-1-hydroxy-2-methylpropyl)cyclohexylamino)-2-oxoethyl)-3-(trifluoromethyl)benzamide te prepared in previous Step (1 eq) in CH2Cl2 (20 mL). The resultant solution was charged with acetone (10 eq) and stirred at RT for 10 min before sodium cyanoborohydride (2 eq) was added in one portion. The reaction was stirred at RT for 10 h and then charged successively with formaldehyde (10 eq in 37 wt % aq soln) and sodium cyanoborohydride (2 eq). The reaction was stirred for another 9 h at RT and then quenched with sat. NaHCO3. The aqueous mixture was extracted with EtOAc (40 mL, then 2×40 mL). The organic extracts were combined, washed with brine (30 mL), dried (MgSO4), filtered, and concentrated in vacuo. After the resulting oil stood, some paraformaldehyde-related products solidified; these were removed by dissolving the mixture in a minimal volume of EtOAc and filtering. Subsequent concentration provided N-(2-((1S,2R,4R)-2-((S)-1-hydroxy-2-methylpropyl)-4-(isopropyl(methyl)amino)cyclohexylamino)-2-oxoethyl)-3-(trifluoromethyl)benzamide. MS found: (M+H)+=472.

Workup

  1. additionwas added in one portion
  2. stirringThe reaction was stirred for another 9 h at RT
  3. customquenched with sat. NaHCO3
  4. extractionThe aqueous mixture was extracted with EtOAc (40 mL
  5. washwashed with brine (30 mL)
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customthese were removed
  10. dissolutionby dissolving the mixture in a minimal volume of EtOAc
  11. filtrationfiltering
  12. concentrationSubsequent concentration

Sources & evidence

ORD record
ord-c84141d80b2d4a7da4bb566c2e395a15
Source dataset
uspto-grants-2008_05
Patent number
US07378409B2

Reaction notes

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