4-Methylmorpholine → tert-butyl N-[[(2S,3S)-3-[[(2S)-4-amino-4-oxo-2-(quinoline-2-carbonylamino)butanoyl]amino]-2-hydroxy-4-phenyl-butyl]-benzyl-amino]carbamate

HRID 1291789Notes

Reaction equation

HRID 1291789 reaction equation
[N:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][C:2]=1[C:11]([NH:13][C@H:14]([C:19]([OH:21])=O)[CH2:15][C:16](=[O:18])[NH2:17])=[O:12].[OH:22][C@H:23]([C@@H:41]([NH2:49])[CH2:42][C:43]1[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=1)[CH2:24][N:25]([CH2:34][C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1)[NH:26][C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28].C1C=CC2N(O)N=NC=2C=1.C1CCC(N=C=NC2CCCCC2)CC1.CN1CCOCC1>C1COCC1>[OH:22][C@H:23]([C@@H:41]([NH:49][C:19](=[O:21])[C@H:14]([CH2:15][C:16](=[O:18])[NH2:17])[NH:13][C:11]([C:2]1[CH:3]=[CH:4][C:5]2[C:10](=[CH:9][CH:8]=[CH:7][CH:6]=2)[N:1]=1)=[O:12])[CH2:42][C:43]1[CH:44]=[CH:45][CH:46]=[CH:47][CH:48]=1)[CH2:24][N:25]([CH2:34][C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1)[NH:26][C:27]([O:29][C:30]([CH3:33])([CH3:31])[CH3:32])=[O:28]

Participants

7

Reactant 5

HCID 79724-MethylmorpholineHCID 10868DicyclohexylcarbodiimideHCID 757711-HydroxybenzotriazoleHCID 11044384(S)-4-Amino-4-oxo-2-(((quinolin-2-yl)carbonyl)amino)butanoic acidHCID 186598251-[2(S)-Hydroxy-3(S)-amino-4-phenyl-butyl]-1-[phenylmethyl]-2-[tert-butoxycarbonyl]-hydrazine

Product 1

HCID 491700tert-butyl N-[[(2S,3S)-3-[[(2S)-4-amino-4-oxo-2-(quinoline-2-carbonylamino)butanoyl]amino]-2-hydroxy-4-phenyl-butyl]-benzyl-amino]carbamate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

At 0° C., 3.84 g (13.4 mmol) of quinoline-2-carbonyl-(L)-asparagine (hydrochloride salt) (Example 100A) b)) are added to 4.69 g (12.2 mmol) of 1-[2(S)-hydroxy-3(S)-amino-4-phenyl-butyl]-1-[phenylmethyl]-2-[tert-butoxycarbonyl]-hydrazine in 250 ml of THF. 2.18 g (13.4 mmol) of HOBT, 2.76 g (13.4 mmol) of DCC and 2.14 ml (19.5 mmol) of NMM are added to the suspension which is then stirred for 30 min at 0° C. and for 17 h at RT. The reaction mixture is filtered and the filtrate is concentrated by evaporation to a residual volume of approximately 50 ml. The fine suspension is taken up in methylene chloride and washed with NaHCO3 solution and brine, and the aqueous phases are extracted with 2 portions of methylene chloride. Filtration of the combined organic phases through cotton wadding, concentration by evaporation and precipitation from a concentrated solution in methanol/methylene chloride with DIPE and finally hexane yields the pure title compound: TLC Rf (P)=0.41; tRet (V)=14.8 min; FAB-MS (M+H)+ =655.

Workup

  1. filtrationThe reaction mixture is filtered
  2. concentrationthe filtrate is concentrated by evaporation to a residual volume of approximately 50 ml
  3. washwashed with NaHCO3 solution and brine
  4. extractionthe aqueous phases are extracted with 2 portions of methylene chloride
  5. filtrationFiltration of the combined organic phases
  6. concentrationthrough cotton wadding, concentration
  7. customby evaporation and precipitation from a concentrated solution in methanol/methylene chloride with DIPE and finally hexane

Sources & evidence

ORD record
ord-eb8371a7893d479b863247ae802141ea
Source dataset
uspto-grants-1998_05
Patent number
US05753652

Reaction notes

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