1,2-Dichloroethane → (2R)-1-Benzyl-N-(3-hydroxy-4-oxo-1-phenyl-4-(pyridin-2-ylmethylamino)-butan-2-yl)-5-oxopyrrolidine-2-carboxamide

HRID 2061679Notes

Reaction equation

HRID 2061679 reaction equation
[CH2:1]([N:8]1[C:12](=[O:13])[CH2:11][CH2:10][C@@H:9]1[C:14]([NH:16][CH:17]([CH2:23][C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)[CH:18]([OH:22])[C:19](O)=[O:20])=[O:15])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[N:30]1[CH:35]=[CH:34][CH:33]=[CH:32][C:31]=1[CH2:36][NH2:37].O.ON1C2C=CC=CC=2N=N1.C(Cl)CCl.C(N(CC)CC)C>ClCCl>[CH2:1]([N:8]1[C:12](=[O:13])[CH2:11][CH2:10][C@@H:9]1[C:14]([NH:16][CH:17]([CH:18]([OH:22])[C:19](=[O:20])[NH:37][CH2:36][C:31]1[CH:32]=[CH:33][CH:34]=[CH:35][N:30]=1)[CH2:23][C:24]1[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=1)=[O:15])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 8471TriethylamineHCID 195092-PyridinemethanamineHCID 27960291-Hydroxybenzotriazole hydrateHCID 666445723-((R)-1-Benzyl-5-oxopyrrolidine-2-carboxamido)-2-hydroxy-4-phenylbutanoic Acid

Product 1

HCID 67095315(2R)-1-Benzyl-N-(3-hydroxy-4-oxo-1-phenyl-4-(pyridin-2-ylmethylamino)-butan-2-yl)-5-oxopyrrolidine-2-carboxamideYield 34%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
5 °C

Procedure

3-((R)-1-benzyl-5-oxopyrrolidine-2-carboxamido)-2-hydroxy-4-phenylbutanoic acid (300 mg, 0.757 mmol) and pyridin-2-ylmethanamine (94 μl, 98 mg, 0.908 mmol) were dissolved in 13 ml dichloromethane and cooled to 5° C. At this temperature 1-hydroxybenzotriazole hydrate (127 mg, 0.832 mmol), EDC (160 mg, 0.832 mmol) and triethylamine (1.58 ml, 127 mg, 1135 mmol) were successively added. After stirring overnight at room temperature the reaction mixture was concentrated under reduced pressure, water was added and the mixture extracted three times with ethyl acetate. The combined organic layers were successively washed with aq. saturated NaHCO3 solution and brine, dried over Na2SO4 and the solvent was removed under reduced pressure. Column chromatography on silica gel using dichloromethane/MeOH (97/3), followed by dichloromethane/MeOH (95/5), resulted in the title compound (125 mg, yield: 34%) as a white powder.

Workup

  1. concentrationwas concentrated under reduced pressure, water
  2. additionwas added
  3. extractionthe mixture extracted three times with ethyl acetate
  4. washThe combined organic layers were successively washed with aq. saturated NaHCO3 solution and brine
  5. dry with materialdried over Na2SO4
  6. customthe solvent was removed under reduced pressure

Sources & evidence

ORD record
ord-e2f17ca2aa7e4995804e116d02a8f7b5
Source dataset
uspto-grants-2012_10
Patent number
US08283363B2

Reaction notes

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