Water → HCID 57815088, compound

HRID 1160462Notes

Reaction equation

HRID 1160462 reaction equation
[CH3:1][N:2]([S:42]([CH3:45])(=[O:44])=[O:43])[C:3]1[CH:4]=[C:5]([CH:28]=[C:29]([C:31]([NH:33][C@@H:34]([C:36]2[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=2)[CH3:35])=[O:32])[CH:30]=1)[C:6]([NH:8][C@@H:9]([CH2:21][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)[C@@H:10]([O:14]C1CCCCO1)[C:11]([OH:13])=O)=[O:7].[NH2:46][C:47]1[NH:48][C:49]2[CH:55]=[CH:54][CH:53]=[CH:52][C:50]=2[N:51]=1.C1C=CC2N(O)N=NC=2C=1.O>CN(C)C1C=CN=CC=1.CN(C)C=O>[CH2:21]([C@H:9]([NH:8][C:6](=[O:7])[C:5]1[CH:4]=[C:3]([N:2]([CH3:1])[S:42]([CH3:45])(=[O:44])=[O:43])[CH:30]=[C:29]([C:31]([NH:33][C@@H:34]([C:36]2[CH:37]=[CH:38][CH:39]=[CH:40][CH:41]=2)[CH3:35])=[O:32])[CH:28]=1)[C@@H:10]([OH:14])[C:11]([NH:46][C:47]1[NH:51][C:50]2[CH:52]=[CH:53][CH:54]=[CH:55][C:49]=2[N:48]=1)=[O:13])[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1

Participants

7

Reactant 4

HCID 962WaterHCID 136242-AminobenzimidazoleHCID 757711-HydroxybenzotriazoleHCID 57815082HCID 57815082, compound

Product 1

HCID 57815088HCID 57815088, compoundYield 48%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6228DimethylformamideSolvent

Procedure

To a 2 mL solution of (2R,3S)-3-{[3-[methyl(methylsulfonyl)amino]-5-({[(1R)-1-phenylethyl]amino}carbonyl)benzoyl]amino}-4-phenyl-2-(tetrahydro-2H-pyran-2-yloxy)butanoic acid obtained in Reference Example 27 64 mg (0.1 mmol), 2-aminobenzimidazole 27 mg (0.2 mmol), HOBt.H2O 31 mg (0.2 mmol) and 4-(dimethylamino)pyridine 2.4 mg (0.02 mmol) in N,N-dimethylformamide was added a polystyrene-supported carbodiimide (1.38 mmol/g) 181 mg (equivalent to carbodiimide 0.25 mmol) and the mixture was shaken overnight. After completion of the reaction, the mixture was filtered and the filtrate was extracted by adding ethyl acetate and 5% aqueous sodium carbonate solution. The organic layer was washed with an aqueous saturated sodium chloride solution and dried on the magnesium sulfate, filtered and concentrated. The concentrated residue was redissolved in chloroform 2 mL and thereto was added TFA 1 mL and the mixture was stirred at room temperature for 3 hours to remove the protecting group. After completion of the reaction, the mixture was concentrated and the concentrated residue was purified by HPLC fraction collector to give 32 mg (0.05 mmol) of the title compound (overall yields: 48%).

Workup

  1. customAfter completion of the reaction
  2. filtrationthe mixture was filtered
  3. extractionthe filtrate was extracted
  4. additionby adding ethyl acetate and 5% aqueous sodium carbonate solution
  5. washThe organic layer was washed with an aqueous saturated sodium chloride solution
  6. dry with materialdried on the magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. dissolutionThe concentrated residue was redissolved in chloroform 2 mL
  10. additionwas added TFA 1 mL
  11. stirringthe mixture was stirred at room temperature for 3 hours
  12. customto remove the protecting group
  13. customAfter completion of the reaction
  14. concentrationthe mixture was concentrated
  15. customthe concentrated residue was purified by HPLC fraction collector

Sources & evidence

ORD record
ord-d672b7a6087f4dbfbbb98ff911bd9307
Source dataset
uspto-grants-2010_10
Patent number
US07816387B2

Reaction notes

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