Diisopropylethylamine → (2R)-N-(4-(Cyclopropylamino)-3-hydroxy-4-oxo-1-phenylbutan-2-yl)-1-(2-methoxy-6-(trifluoromethyl)benzyl)-5-oxopyrrolidine-2-carboxamide

HRID 1474146Notes

Reaction equation

HRID 1474146 reaction equation
CCN(C(C)C)C(C)C.[CH3:10][O:11][C:12]1[CH:27]=[CH:26][CH:25]=[C:24]([C:28]([F:31])([F:30])[F:29])[C:13]=1[CH2:14][N:15]1[C:19](=[O:20])[CH2:18][CH2:17][C@@H:16]1[C:21](O)=[O:22].Cl.[NH2:33][CH:34]([CH2:43][C:44]1[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=1)[CH:35]([OH:42])[C:36]([NH:38][CH:39]1[CH2:41][CH2:40]1)=[O:37].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>C(Cl)Cl.O>[CH:39]1([NH:38][C:36](=[O:37])[CH:35]([OH:42])[CH:34]([NH:33][C:21]([C@H:16]2[CH2:17][CH2:18][C:19](=[O:20])[N:15]2[CH2:14][C:13]2[C:24]([C:28]([F:31])([F:29])[F:30])=[CH:25][CH:26]=[CH:27][C:12]=2[O:11][CH3:10])=[O:22])[CH2:43][C:44]2[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=2)[CH2:40][CH2:41]1

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 66644853(R)-1-(2-methoxy-6-(trifluoromethyl)benzyl)-5-oxopyrrolidine-2-carboxylic acidHCID 666450253-Amino-N-cyclopropyl-2-hydroxy-4-phenylbutanamide Hydrochloride

Product 1

HCID 67095048(2R)-N-(4-(Cyclopropylamino)-3-hydroxy-4-oxo-1-phenylbutan-2-yl)-1-(2-methoxy-6-(trifluoromethyl)benzyl)-5-oxopyrrolidine-2-carboxamideYield 126.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent2×

Procedure

DIPEA (0.8 ml, 4.58 mmol) was added to a mixture of (R)-1-(2-methoxy-6-(trifluoromethyl)benzyl)-5-oxopyrrolidine-2-carboxylic acid (234 mg, 0.74 mmol) and 3-amino-N-cyclopropyl-2-hydroxy-4-phenylbutanamide hydrochloride (200 mg, 0.74 mmol) in DCM (50 mL). After stirring for 10 min HATU (337 mg, 0.89 mmol) was added and the stirring was continued overnight. The reaction mixture was diluted with DCM and water was added. The organic layer was separated and the aqueous layer was extracted with DCM. The combined organic layers were washed with saturated aqueous NaHCO3 solution, saturated aqueous NaCl solution and dried over MgSO4. Removal of the solvent in vacuo provided the title compound (498 mg, 95%, ca. 75% purity).

Workup

  1. additionwas added
  2. additionwas added
  3. customThe organic layer was separated
  4. extractionthe aqueous layer was extracted with DCM
  5. washThe combined organic layers were washed with saturated aqueous NaHCO3 solution, saturated aqueous NaCl solution
  6. dry with materialdried over MgSO4
  7. customRemoval of the solvent in vacuo

Sources & evidence

ORD record
ord-ac4b7085d96341119bc82b61e5053fb6
Source dataset
uspto-grants-2015_04
Patent number
US09018206B2

Reaction notes

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