Dimethylformamide → methyl N-[(1S)-1-[[(1S,2R)-1-benzyl-3-[cyclohexylmethyl-[[(2S)-2-(methoxycarbonylamino)-3-methyl-butanoyl]amino]amino]-2-hydroxy-propyl]carbamoyl]-2-methyl-propyl]carbamate

HRID 1291780Notes

Reaction equation

HRID 1291780 reaction equation
[CH3:1][O:2][C:3]([NH:5][C@H:6]([C:10]([OH:12])=O)[CH:7]([CH3:9])[CH3:8])=[O:4].F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)[C:24]2C=CC=[CH:28][C:23]=2N=N1.C1C=CC2N([OH:49])N=NC=2C=1.C[N:51]1[CH2:56][CH2:55][O:54]C[CH2:52]1.[OH:57][C@@H:58]([C@@H:69]([NH2:77])[CH2:70][C:71]1[CH:76]=[CH:75][CH:74]=[CH:73][CH:72]=1)[CH2:59][N:60]([CH2:62][CH:63]1[CH2:68][CH2:67][CH2:66][CH2:65][CH2:64]1)[NH2:61].CN([CH:81]=[O:82])C>>[OH:57][C@@H:58]([C@@H:69]([NH:77][C:10](=[O:12])[C@H:6]([CH:7]([CH3:8])[CH3:9])[NH:5][C:3]([O:2][CH3:1])=[O:4])[CH2:70][C:71]1[CH:72]=[CH:73][CH:74]=[CH:75][CH:76]=1)[CH2:59][N:60]([CH2:62][CH:63]1[CH2:64][CH2:65][CH2:66][CH2:67][CH2:68]1)[NH:61][C:55](=[O:54])[C@H:56]([CH:23]([CH3:28])[CH3:24])[NH:51][C:52]([O:82][CH3:81])=[O:49]

Participants

7

Reactant 6

HCID 6228DimethylformamideHCID 79724-MethylmorpholineHCID 757711-HydroxybenzotriazoleHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 10756020HCID 10756020, compoundHCID 10942966(2S)-2-((methoxycarbonyl)amino)-3-methylbutanoic acid

Product 1

HCID 461982methyl N-[(1S)-1-[[(1S,2R)-1-benzyl-3-[cyclohexylmethyl-[[(2S)-2-(methoxycarbonylamino)-3-methyl-butanoyl]amino]amino]-2-hydroxy-propyl]carbamoyl]-2-methyl-propyl]carbamate

Procedure

Under a protective gas atmosphere, 33 mg (0.186 mmol) of N-methoxycarbonyl-(L)-valine (Example 73b) are activated with 82 mg (0.186 mmol) of BOP and 25 mg (0.186 mmol) of HOBT in 1.24 ml of a 0.3M solution of NMM in DMF and, after 15 min, reacted with 25 mg (0.062 mmol) of 1-[2(R)-hydroxy-3(S)-amino-4-phenyl-butyl]-1-[cyclohexylmethyl]-hydrazine (in the form of the hydrochloride salt) for 18 h. The reaction mixture is concentrated by evaporation under HV and the residue is partitioned between 3 portions of methylene chloride, 2 portions of saturated NaHCO3 solution and brine. Column chromatography (Si2, methylene chloride/methanol 99:1→15:1) and precipitation with DIPE from a concentrated solution in DMF yields the pure title compound: tRet (V)=14.7 min; FAB-MS (M+H)+ =606.

Workup

  1. concentrationThe reaction mixture is concentrated by evaporation under HV
  2. customthe residue is partitioned between 3 portions of methylene chloride, 2 portions of saturated NaHCO3 solution and brine
  3. customColumn chromatography (Si2, methylene chloride/methanol 99:1→15:1) and precipitation with DIPE from a concentrated solution in DMF

Sources & evidence

ORD record
ord-880f52a69de84f519df5e7f4694634a9
Source dataset
uspto-grants-1998_05
Patent number
US05753652

Reaction notes

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