1,2-Dichloroethane → 3(S)-(2-((2(S)-Benzoylamino-3-methylbutyryl)benzylamino)acetylamino)-4-oxo-butyric Acid tert-Butyl Ester Semicarbazone

HRID 1456649Notes

Reaction equation

HRID 1456649 reaction equation
[C:1]([O:5][C:6](=[N:29][NH:30][C:31]([NH2:33])=[O:32])[CH2:7][C@H:8]([NH:11]C(OCC1C2CC3C(=CC=CC=3)C=2C=CC=1)=O)[CH:9]=[O:10])([CH3:4])([CH3:3])[CH3:2].C(NCC)C.[C:39]([NH:47][C@@H:48]([CH:63]([CH3:65])[CH3:64])[C:49]([N:51]([CH2:59][C:60]([OH:62])=O)[CH2:52][C:53]1[CH:58]=[CH:57][CH:56]=[CH:55][CH:54]=1)=[O:50])(=[O:46])[C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1.C1C=CC2N(O)N=NC=2C=1.C(Cl)CCl>C(#N)C.CCOC(C)=O.O.CN(C=O)C.C(Cl)Cl>[C:1]([O:5][C:6](=[N:29][NH:30][C:31]([NH2:33])=[O:32])[CH2:7][C@H:8]([NH:11][C:60](=[O:62])[CH2:59][N:51]([C:49](=[O:50])[C@@H:48]([NH:47][C:39](=[O:46])[C:40]1[CH:41]=[CH:42][CH:43]=[CH:44][CH:45]=1)[CH:63]([CH3:64])[CH3:65])[CH2:52][C:53]1[CH:54]=[CH:55][CH:56]=[CH:57][CH:58]=1)[CH:9]=[O:10])([CH3:4])([CH3:2])[CH3:3]

Participants

11

Reactant 5

HCID 111,2-DichloroethaneHCID 8021DiethylamineHCID 757711-HydroxybenzotriazoleHCID 53859725((2(S)-Benzoylamino-3-methylbutyryl)benzylamino)acetic AcidHCID 566185953(S)-(1-fluorenylmethyloxycarbonylamino)-4-oxobutyric acid tert-butyl ester semicarbazone

Product 1

HCID 545745803(S)-(2-((2(S)-Benzoylamino-3-methylbutyryl)benzylamino)acetylamino)-4-oxo-butyric Acid tert-Butyl Ester Semicarbazone

Reagents, catalysts & solvents 5

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 3(S)-(1-fluorenylmethyloxycarbonylamino)-4-oxobutyric acid tert-butyl ester semicarbazone (678 mg, 1.5 mmol; Prepared in a similar manner to the benzyloxycarbonyl analog in Graybill et al., Int. J. Protein Res. , 44, pp. 173-82 (1994)) in acetonitrile (5.0 mL) was added diethylamine (780 μL, 7.5 mmol) and the reaction allowed to stir at rt for 1 hr. The reaction was concentrated in vacuo and the residue co-concentrated with toluene (3×) in vacuo. To a suspension of the residue, compound 704 (555 mg, 1.5 mmol) and HOBT (224 mg, 1.66 mmol) in 1:1 CH2Cl2 :DMF (10 mL) at 0° C., was added EDC (318 mg, 1.66 mmol). The reaction was warmed to rt and stirred over night. The reaction was diluted with EtOAc and H2O. The layers were separated and the organic phase washed with sat. aq. NaHCO3, sat. aq. KHSO4, brine, dried over MgSO4, filtered and concentrated in vacuo. Chromatography of the residue on silica gel (elution with 2-6% MeOH:CH2Cl2) provided 600 mg of compound 705. ##STR84##

Workup

  1. concentrationThe reaction was concentrated in vacuo
  2. temperatureThe reaction was warmed to rt
  3. stirringstirred over night
  4. customThe layers were separated
  5. washthe organic phase washed with sat. aq. NaHCO3, sat. aq. KHSO4, brine
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-72025e5cced5432db4183b6fd4b8f560
Source dataset
uspto-grants-1998_12
Patent number
US05843904

Reaction notes

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