Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1) → 1-[2(S)-Hydroxy-3(S)-(N-(quinoline-2-carbonyl)-(L)-asparaginyl)amino-4-phenyl-butyl]-1-[phenylmethyl]-2-[N-(methoxy-ethoxy-ethoxycarbonyl)-(L)-valyl]-hydrazine

HRID 1291798Notes

Reaction equation

HRID 1291798 reaction equation
CO[CH2:3][CH2:4][O:5][CH2:6][CH2:7][O:8][C:9]([NH:11][C@H:12]([C:16]([OH:18])=O)[CH:13]([CH3:15])[CH3:14])=[O:10].[OH:19][C@H:20]([C@@H:31]([NH:39][C:40](=[O:59])[C@H:41]([CH2:55][C:56](=[O:58])[NH2:57])[NH:42][C:43]([C:45]1[CH:54]=[CH:53][C:52]2[C:47](=[CH:48][CH:49]=[CH:50][CH:51]=2)[N:46]=1)=[O:44])[CH2:32][C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1)[CH2:21][N:22]([CH2:24][C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)[NH2:23].CN([C:63]([O:67]N1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN1CCOCC1.CN(C=O)C.C(Cl)Cl>[OH:19][C@H:20]([C@@H:31]([NH:39][C:40](=[O:59])[C@H:41]([CH2:55][C:56](=[O:58])[NH2:57])[NH:42][C:43]([C:45]1[CH:54]=[CH:53][C:52]2[C:47](=[CH:48][CH:49]=[CH:50][CH:51]=2)[N:46]=1)=[O:44])[CH2:32][C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1)[CH2:21][N:22]([CH2:24][C:25]1[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=1)[NH:23][C:16](=[O:18])[C@H:12]([CH:13]([CH3:14])[CH3:15])[NH:11][C:9]([O:8][CH2:7][CH:6]([O:67][CH3:63])[O:5][CH2:4][CH3:3])=[O:10]

Participants

6

Reactant 3

HCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 54169760N-(2-(2-Methoxyethoxy)-ethoxy)carbonyl-(L)-valineHCID 697828951-[2(S)-Hydroxy-3(S)-(N-(quinoline-2-carbonyl)-(L)-asparaginyl)amino-4-phenylbutyl]-1-[phenylmethyl]-hydrazine

Product 1

HCID 1317206601-[2(S)-Hydroxy-3(S)-(N-(quinoline-2-carbonyl)-(L)-asparaginyl)amino-4-phenyl-butyl]-1-[phenylmethyl]-2-[N-(methoxy-ethoxy-ethoxycarbonyl)-(L)-valyl]-hydrazine

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 19048625Dmf nmmSolvent

Procedure

Analogously to Example 111, 52 mg (0.198 mmol) of N-(2-(2-methoxy-ethoxy)-ethoxy)carbonyl-(L)-valine (Example 82a)) and 100 mg (0.180 mmol) of 1-[2(S)-hydroxy-3(S)-(N-(quinoline-2-carbonyl)-(L)-asparaginyl)amino-4-phenyl-butyl]-1-[phenylmethyl]-hydrazine in 1.8 ml of 0.3M NMM/DMF are reacted with 75.1 mg (0.198 mmol) of HBTU. The evaporation residue is taken up in methylene chloride and washed with 2 portions of 10% citric acid solution, water, saturated NaHCO3 solution and brine. The aqueous phases are extracted a further twice with methylene chloride and the combined organic phases are dried with Na2SO4 and concentrated by evaporation. Column chromatography (SiO2, methylene chloride/methanol 19:1) yields the title compound: TLC Rf (J')=0.08; tRet (V)=13.5 min; FAB-MS (M+H)+ +800.

Workup

  1. washwashed with 2 portions of 10% citric acid solution, water, saturated NaHCO3 solution and brine
  2. extractionThe aqueous phases are extracted a further twice with methylene chloride
  3. dry with materialthe combined organic phases are dried with Na2SO4
  4. concentrationconcentrated by evaporation

Sources & evidence

ORD record
ord-43fc557bfd2b4c69804073f28e5b88ea
Source dataset
uspto-grants-1998_05
Patent number
US05753652

Reaction notes

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