HCID 86594360, compound → HCID 69034585, compound

HRID 1391867Notes

Reaction equation

HRID 1391867 reaction equation
[C:1]([O:5][C:6](=[O:35])[NH:7][C@H:8]1[CH2:12][CH2:11][N:10]([C@H:13]2[CH2:18][CH2:17][C@@H:16]([N:19]=[N+]=[N-])[CH2:15][C@H:14]2[CH2:22][S:23]([C:26]2[CH:31]=[CH:30][C:29]([S:32][CH3:33])=[CH:28][CH:27]=2)(=[O:25])=[O:24])[C:9]1=[O:34])([CH3:4])([CH3:3])[CH3:2].[H][H]>CO.[Pd].[O-]S([O-])(=O)=O.[Ba+2]>[C:1]([O:5][C:6](=[O:35])[NH:7][C@H:8]1[CH2:12][CH2:11][N:10]([C@H:13]2[CH2:18][CH2:17][C@@H:16]([NH2:19])[CH2:15][C@H:14]2[CH2:22][S:23]([C:26]2[CH:31]=[CH:30][C:29]([S:32][CH3:33])=[CH:28][CH:27]=2)(=[O:25])=[O:24])[C:9]1=[O:34])([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 2

HCID 86594360HCID 86594360, compoundHCID 178418361HCID 178418361, compound

Product 1

HCID 69034585HCID 69034585, compoundYield 149.4%

Reagents, catalysts & solvents 2

HCID 16218511Pd barium sulfateCatalystHCID 887MethanolSolvent

Procedure

{(3S)-1-[(1S,2R,4R)-4-Azido-2-(4-methylsulfanyl-benzenesulfonylmethyl)-cyclohexyl]-2-oxo-pyrrolidin-3-yl}-carbamic acid tert-butyl ester (350 mg), from the synthesis of Example 17 (analogous to 10f), was dissolved in MeOH (5 mL) prior to the addition of 5% Pd/BaSO4 (300 mg). A hydrogen balloon was added and the mixture was stirred. After stirring 1 h, the Pd/BaSO4 was filtered off and the solvent was concentrated to give {(3S)-1-[(1S,2R,4R)-4-amino-2-(4-methylsulfanyl-benzenesulfonylmethyl)-cyclohexyl]-2-oxo-pyrrolidin-3-yl}-carbamic acid tert-butyl ester (497 mg). MS found: (M−H)−=496.5. (18b) A portion of the above material (341 mg) was dissolved in dichloroethane (5 mL) prior to the adddition of acetone (0.25 mL) and NaBH(OAc)3 (436 mg). After 2 h, the solution was concentrated. The resulting residue was dissolved in EtOAc and washed with saturated NaHCO3. The organic layer was dried, filtered, and concentrated. The resulting residue was dissolved in MeOH (2 mL) prior to the addition of 37% formaldehyde in water (0.1 mL). After 15 min, NaBH3CN (111 mg) was added. After 2 h, saturated NaHCO3 was added and some of the MeOH was removed. EtOAc was added and the organic layer was dried, filtered, and concentrated. This material was passed through a plug of silica and concentrated. This material (300 mg) was dissolved in CH2Cl2 (5 mL) prior to the addition of TFA (2.5 mL). After 30 min, it was concentrated and dried. A portion of the resulting residue (35 mg) was dissolved in DMF (1 mL) prior to the addition of 4-methylmorpholine (0.02 mL) and 3-trifluoromethylphenyl isocyanate (0.013 mL). After 2 h, the solution was concentrated. Reverse phase HPLC purification (gradient elution, water/acetonitrile/TFA) of the resulting residue provided the title compound (7 mg). MS found: (M+H)+=641.3.

Workup

  1. stirringAfter stirring 1 h
  2. filtrationthe Pd/BaSO4 was filtered off
  3. concentrationthe solvent was concentrated

Sources & evidence

ORD record
ord-69730b4781da40aab143517f32bf4b4b
Source dataset
uspto-grants-2008_03
Patent number
US07338947B2

Reaction notes

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