1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → (1S,5S)-(1-{5-[(4-amino-benzenesulfonyl)-isobutyl-amino]-6-phosphonooxy hexylcarbamoyl}-2,2-diphenyl-ethyl)-carbamic acid methyl ester

HRID 132700Notes

Reaction equation

HRID 132700 reaction equation
[CH3:1][O:2][C:3]([NH:5][C@@H:6]([CH:10]([C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)[C:7](O)=[O:8])=[O:4].CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.C([O:46][P:47](=[O:74])([O:71]CC)[O:48][CH2:49][C@@H:50]([N:56]([S:61]([C:64]1[CH:69]=[CH:68][C:67]([NH2:70])=[CH:66][CH:65]=1)(=[O:63])=[O:62])[CH2:57][CH:58]([CH3:60])[CH3:59])[CH2:51][CH2:52][CH2:53][CH2:54][NH2:55])C>CN(C=O)C>[CH3:1][O:2][C:3](=[O:4])[NH:5][C@H:6]([C:7](=[O:8])[NH:55][CH2:54][CH2:53][CH2:52][CH2:51][C@H:50]([N:56]([S:61]([C:64]1[CH:65]=[CH:66][C:67]([NH2:70])=[CH:68][CH:69]=1)(=[O:62])=[O:63])[CH2:57][CH:58]([CH3:60])[CH3:59])[CH2:49][O:48][P:47]([OH:71])([OH:46])=[O:74])[CH:10]([C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1

Participants

6

Reactant 4

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 10017620(S)-2-methoxycarbonylamino-3,3-diphenyl-propionic acidHCID 59733921(2S)-phosphoric acid 6-amino-2-[(4-amino-benzenesulfonyl)-isobutyl-amino]-hexyl ester diethyl ester

Product 1

HCID 11563875(1S,5S)-(1-{5-[(4-amino-benzenesulfonyl)-isobutyl-amino]-6-phosphonooxy hexylcarbamoyl}-2,2-diphenyl-ethyl)-carbamic acid methyl esterYield 139.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

(2S)-2-methoxycarbonylamino-3,3-diphenyl-propionic acid ((example 1, step E) 0.9 g, 3 mmol) was activated in DMF (5 mL) with EDAC (1.7 g, 9 mmol) and HOBt (1.2 g, 9 mmol). To the solution was added 1.17 g of (2S)-phosphoric acid 6-amino-2-[(4-amino -benzenesulfonyl)-isobutyl-amino]-hexyl ester diethyl ester (1X) (example 3, step B) and the mixture stirred for 3 h. 20 g of Amberlite XAD-2 resin was then added and the beads were left to soak for 10 min. The resin was transferred into a glass filter and washed thoroughly with distilled water (400 mL) and 200 mL of 1M NaHCO3. The beads were then washed with 4×50 ml portions of MeOH then EtOAc 200 mL. The organic phase was evaporated. The residue was adsorbed onto silica gel and passed through a short silica gel column (EtOAc) to yield 2.4 g (83%) of white solid after evaporation.

Workup

  1. addition20 g of Amberlite XAD-2 resin was then added
  2. waitthe beads were left
  3. waitto soak for 10 min
  4. filtrationfilter
  5. washwashed thoroughly with distilled water (400 mL) and 200 mL of 1M NaHCO3
  6. washThe beads were then washed with 4×50 ml portions of MeOH
  7. customThe organic phase was evaporated

Sources & evidence

ORD record
ord-3e86046866034a439a328c075f181b75
Source dataset
uspto-grants-2008_06
Patent number
US07388008B2

Reaction notes

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