p-Toluenesulfonic acid → HCID 57672294, compound

HRID 1675181Notes

Reaction equation

HRID 1675181 reaction equation
[NH2:1][C@@H:2]([C@@H:11]([OH:28])[C@@H:12]([NH:20][C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)[C:3]([NH:5][CH:6]([CH3:10])[CH2:7][CH2:8][CH3:9])=[O:4].[C:29]1([CH3:39])[CH:34]=CC(S(O)(=O)=O)=C[CH:30]=1.[O-]S([O-])(=O)=O.[Na+].[Na+]>CO>[CH2:13]([C@H:12]([NH:20][C:21](=[O:22])[O:23][C:24]([CH3:26])([CH3:25])[CH3:27])[C@H:11]([OH:28])[C@H:2]1[C:3](=[O:4])[N:5]([CH:6]([CH3:10])[CH2:7][CH2:8][CH3:9])[CH:30]([CH:29]([CH3:39])[CH3:34])[NH:1]1)[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1

Participants

5

Reactant 3

HCID 6101p-Toluenesulfonic acidHCID 24436Sodium SulfateHCID 57433088HCID 57433088, compound

Product 1

HCID 57672294HCID 57672294, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
65 °C

Procedure

To a solution of (2S,3R,4S)-2-amino-4-[(tert-butoxycarbonyl)amino]-3-hydroxy-N-(1-methylbutyl)-5-phenylpentanamide (46 mg, 0.117 mmol) in MeOH (500 mL) was added isobutylaldehyde (100 mL), a small amount of p-toluene sulfonic acid, and Na2SO4 (10 mg). The mixture was capped and heated to 65° C. overnight. The reaction was filtered and the resulting filtrate purified by reverse phase chromatography on a C-18 column using a gradient elution of 95-5% H2O (0.1% TFA)/CH3CN (0.1% TFA). Collection and concentration of the appropriate fractions separately afforded the earlier and later eluting diastereomer products as the trifluoroacetate salts. Earlier eluting diastereomer: 1H NMR (400 MHz, CD3OD) δ 7.29-7.25 (m, 4H), 7.19-7.18 (m, 1H), 4.23 (br s, 1H), 4.05-3.88 (m, 2H), 3.75-3.63 (m, 1H), 3.15-3.05 (m, 1H), 2.80-2.74 (m, 1H), 2.33-2.27 (m, 1H), 1.98 -1.89 (m, 1H), 1.76-1.70 (m, 1H), 1.60-1.51 (m, 1H), 1.48-1.24 (m, 11H), 1.22-1.20 (m, 2H), 1.13 -1.08 (m, 4H), 0.99-0.87 (m, 6H); HRMS (FT-ICR) C25H41N3O4+H=448.3195; calculated 448.3170; Later eluting diastereomer: 1H NMR (400 MHz, CD3OD) δ 7.28-7.25 (m, 4H), 7.19-7.18 (m, 1H), 4.26-4.24 (m, 1H), 4.08-3.99 (m, 2H), 3.77-3.70 (m, 1H), 3.10-3.07 (m, 1H), 2.83 -2.77 (m, 1H), 2.38-2.37 (m, 1H), 1.85-1.77 (m, 2H), 1.62-1.56 (m, 1H), 1.42-1.27 (m, 11H), 1.24 (m, 3H), 1.11 (t, J=5.6 Hz, 3H), 1.02 (d, J=6.8 Hz, 3H), 0.99-0.93 (m, 3H); HRMS (FT-ICR) C25H41N3O4+H=448.3168; calculated 448.3170.

Workup

  1. customThe mixture was capped
  2. filtrationThe reaction was filtered
  3. customthe resulting filtrate purified by reverse phase chromatography on a C-18 column
  4. washa gradient elution of 95-5% H2O (0.1% TFA)/CH3CN (0.1% TFA)
  5. customCollection and concentration of the appropriate fractions
  6. customseparately afforded the earlier and
  7. washlater eluting diastereomer products as the trifluoroacetate salts
  8. washEarlier eluting diastereomer
  9. washLater eluting diastereomer

Sources & evidence

ORD record
ord-422b376c789c4ffab6cc39e5e7a7c17d
Source dataset
uspto-grants-2011_08
Patent number
US08003653B2

Reaction notes

Loading…