1,2-Dichloroethane → HCID 67343769, compound

HRID 1670034Notes

Reaction equation

HRID 1670034 reaction equation
OC(C(F)(F)F)=O.[NH2:8][C@H:9]([CH2:30][C:31]1[CH:36]=[CH:35][C:34]([Cl:37])=[CH:33][CH:32]=1)[C:10]([NH:12][N:13]1[CH2:17][CH2:16][C@H:15]([N:18]([CH:24]2[CH2:29][CH2:28][CH2:27][CH2:26][CH2:25]2)[C:19](=[O:23])[CH:20]([CH3:22])[CH3:21])[CH2:14]1)=[O:11].CCN(C(C)C)C(C)C.C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.[C:61]([N:68]1[CH2:75][CH2:74][CH2:73][C@@H:69]1[C:70](O)=[O:71])([O:63][C:64]([CH3:67])([CH3:66])[CH3:65])=[O:62]>CN(C=O)C>[C:61]([N:68]1[CH2:75][CH2:74][CH2:73][C@@H:69]1[C:70]([NH:8][C@H:9]([CH2:30][C:31]1[CH:36]=[CH:35][C:34]([Cl:37])=[CH:33][CH:32]=1)[C:10]([NH:12][N:13]1[CH2:17][CH2:16][C@H:15]([N:18]([CH:24]2[CH2:29][CH2:28][CH2:27][CH2:26][CH2:25]2)[C:19](=[O:23])[CH:20]([CH3:22])[CH3:21])[CH2:14]1)=[O:11])=[O:71])([O:63][C:64]([CH3:67])([CH3:66])[CH3:65])=[O:62]

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 688022(2R)-1-[(tert-butoxy)carbonyl]pyrrolidine-2-carboxylic acidHCID 86612824HCID 86612824, compound

Product 1

HCID 67343769HCID 67343769, compoundYield 90.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of (2R)-2-amino-N-{(3S)-3-[cyclohexyl(isobutyryl)amino]pyrrolidine-1-yl}-3-(4-chlorophenyl)propionamide TFA, prepared in Example 1, (100 mg, 0.188 mmol) in DMF (3 mL) were added DIPEA (66.1 mL, 0.381 mmol), EDC (48.7 mg, 0.252 mmol), HOBT (43.6 mg, 0.322 mmol), and (2R)-N-BOC-proline (40.9 mg, 0.190 mmol). After the reaction mixture was stirred at rt for 12 h, DMF was removed in vacuo, and the residue was diluted with a saturated aqueous NaHCO3 solution and EtOAc. The organic layer was extracted with EtOAc and subsequently washed with a saturated aqueous NaHCO3 solution, water and an aqueous 1N HCl solution. The organic solution was dried over MgSO4 and concentrated in vacuo. The residue was purified by column chomatography (eluent: EtOAc/Hex=2/1) to give the title compound (107 g, 90.8%).

Workup

  1. customDMF was removed in vacuo
  2. additionthe residue was diluted with a saturated aqueous NaHCO3 solution and EtOAc
  3. extractionThe organic layer was extracted with EtOAc
  4. washsubsequently washed with a saturated aqueous NaHCO3 solution, water
  5. dry with materialThe organic solution was dried over MgSO4
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by column chomatography (eluent: EtOAc/Hex=2/1)

Sources & evidence

ORD record
ord-5a68b265452c44bc883a831b68b0eaa1
Source dataset
uspto-grants-2011_08
Patent number
US07989634B2

Reaction notes

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