4-Methylmorpholine → HCID 69783948, compound

HRID 1291782Notes

Reaction equation

HRID 1291782 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].Cl.[OH:79][C@H:80]([C@@H](N)CC1C=CC=CC=1)CN(CC1CCCCC1)N>CN(C=O)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:79][CH3:80])=[O:49]

Participants

8

Reactant 6

HCID 79724-MethylmorpholineHCID 757711-HydroxybenzotriazoleHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 10942966(2S)-2-((methoxycarbonyl)amino)-3-methylbutanoic acidHCID 18659804HCID 18659804, compoundHCID 18659824HCID 18659824, compound

Product 1

HCID 69783948HCID 69783948, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Under a nitrogen atmosphere, 315 mg (1.80 mmol) of N-methoxycarbonyl-(L)-valine (Example 73b) are activated with 795 mg (1.80 mmol) of BOP and 267 mg (1.80 mmol) of HOBT in 12 ml of a 0.3M solution of NMM in DMF and, after 15 min, reacted for 48 h with 240 mg (0.60 mmol) of 1-[2(R)-hydroxy-3(R)-amino-4-phenyl-butyl]-1-[cyclohexylmethyl]-hydrazine (in the form of the hydrochloride salt) (can be prepared analogously to 1-[2(S)-hydroxy-3(S)-amino-4-phenyl-butyl]-1-[cyclohexylmethyl]-hydrazine hydrochloride salt (Example 10a, =H-[PheNNCha]-H.3HCl) from (D)-N-Boc-phenylalanine). 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 (SiO2, methylene chloride/methanol 19:1) and digestion with methylene chloride/DIPE yields the pure title compound: TLC Rf (B')=0.60; 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

Sources & evidence

ORD record
ord-ae51f2f9541f4fd3886971c462819691
Source dataset
uspto-grants-1998_05
Patent number
US05753652

Reaction notes

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