1,2-Dichloroethane → HCID 9873648, compound

HRID 396581Notes

Reaction equation

HRID 396581 reaction equation
[N:1]1([C:7]([NH:9][C@H:10]([C:15]([OH:17])=O)[CH2:11][CH:12]([CH3:14])[CH3:13])=[O:8])[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.C(OC(=O)[NH:38][CH:39]([C:48]([C:50]1[O:54][C:53]([C:55]2[CH:60]=[CH:59][CH:58]=[CH:57][CH:56]=2)=[N:52][C:51]=1[C:61]1[CH:66]=[CH:65][CH:64]=[CH:63][CH:62]=1)=[O:49])[CH2:40][CH2:41][C:42]1[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=1)(C)(C)C.C(O)(C(F)(F)F)=O.CN1CCOCC1.N[C@H](C(O)=O)CC(C)C>CN(C=O)C.C(Cl)Cl>[C:55]1([C:53]2[O:54][C:50]([C:48]([C@@H:39]([NH:38][C:15]([C@@H:10]([NH:9][C:7]([N:1]3[CH2:2][CH2:3][O:4][CH2:5][CH2:6]3)=[O:8])[CH2:11][CH:12]([CH3:13])[CH3:14])=[O:17])[CH2:40][CH2:41][C:42]3[CH:43]=[CH:44][CH:45]=[CH:46][CH:47]=3)=[O:49])=[C:51]([C:61]3[CH:66]=[CH:65][CH:64]=[CH:63][CH:62]=3)[N:52]=2)[CH:56]=[CH:57][CH:58]=[CH:59][CH:60]=1

Participants

10

Reactant 7

HCID 111,2-DichloroethaneHCID 6106L-LeucineHCID 6422Trifluoroacetic acidHCID 79724-MethylmorpholineHCID 757711-HydroxybenzotriazoleHCID 938788HCID 938788, compoundHCID 69900713HCID 69900713, compound

Product 1

HCID 9873648HCID 9873648, compoundYield 84%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

N-[(4-Morpholinyl)carbonyl]-L-leucine (100 mg, 0.35 mmol) (prepared as described in Example 1) was dissolved in 10 mL DMF and cooled to 0° C. To the solution was added EDC (77 mg, 0.4 mmol) and HOBt (54 mg, 0.4 mmol) and the reaction was stirred for 1 h. In a separate flask, [1-(2,4-diphenyloxazole-5-carbonyl)-3-phenylpropyl]carbamic acid tert-butyl ester (158 mg, 0.31 mmol) was dissolved in 4 mL CH2Cl2 and 2 mL TFA was added. After stirring for 1 h, the solvents were evaporated, the residue was dissolved in 5 mL DMF and N-methylmorpholine (406 mg, 0.4 mmol) was added. The resulting solution was added to the previously prepared solution of activated leucine derivative at 0° C. The reaction mixture was stirred at room temperature for 3 h, cooled to 0° C., and quenched with 100 mL of a 10% solution of citric acid in water. The resulting mixture was extracted with 3×100 mL EtOAc. The combined organic extracts were washed with 2×100 mL of saturated bicarbonate and 1×100 mL brine. The organic layer was dried over Na2SO4, filtered and concentrated to a residue that was purified by chromatography (florisil, 30%-50% EtOAc in hexane) to give the title compound as a white solid (90 mg, 84%), m.p. 83-5° C., MS (ES) 609 (M+).

Workup

  1. stirringAfter stirring for 1 h
  2. customthe solvents were evaporated
  3. dissolutionthe residue was dissolved in 5 mL DMF
  4. stirringThe reaction mixture was stirred at room temperature for 3 h
  5. temperaturecooled to 0° C.
  6. customquenched with 100 mL of a 10% solution of citric acid in water
  7. extractionThe resulting mixture was extracted with 3×100 mL EtOAc
  8. washThe combined organic extracts were washed with 2×100 mL of saturated bicarbonate and 1×100 mL brine
  9. dry with materialThe organic layer was dried over Na2SO4
  10. filtrationfiltered
  11. concentrationconcentrated to a residue that
  12. customwas purified by chromatography (florisil, 30%-50% EtOAc in hexane)

Sources & evidence

ORD record
ord-e4db6cf4a9004a7aa3d544b61b20b1e7
Source dataset
uspto-grants-2003_08
Patent number
US06608057B2

Reaction notes

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