1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → Di-tert-butyl (2S)-2-[(3-{[5-oxido-4-(phenylsulphonyl)-1,2,5-oxadiazol-3-yl]-oxy}-propionyl)-amino]-pentanedioate

HRID 1013434Notes

Reaction equation

HRID 1013434 reaction equation
[O-:1][N+:2]1[O:6][N:5]=[C:4]([O:7][CH2:8][CH2:9][C:10]([OH:12])=O)[C:3]=1[S:13]([C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)(=[O:15])=[O:14].[NH2:22][C@H:23]([C:29]([OH:31])=[O:30])[CH2:24][CH2:25][C:26]([OH:28])=[O:27].[C:32]([ClH]C(C)(C)C)([CH3:35])([CH3:34])[CH3:33].CCN=C=N[CH2:46][CH2:47][CH2:48]N(C)C.[CH3:52]CN(C(C)C)C(C)C.C1C=CC2N(O)N=NC=2C=1>CN(C=O)C>[O-:1][N+:2]1[O:6][N:5]=[C:4]([O:7][CH2:8][CH2:9][C:10]([NH:22][C@@H:23]([CH2:24][CH2:25][C:26]([O:28][C:47]([CH3:48])([CH3:52])[CH3:46])=[O:27])[C:29]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30])=[O:12])[C:3]=1[S:13]([C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)(=[O:15])=[O:14]

Participants

6

Reactant 4

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 576261723-[[4-(Benzenesulfonyl)-5-oxido-1,2,5-oxadiazol-5-ium-3-yl]oxy]propanoic acid

Product 1

HCID 67317279Di-tert-butyl (2S)-2-[(3-{[5-oxido-4-(phenylsulphonyl)-1,2,5-oxadiazol-3-yl]-oxy}-propionyl)-amino]-pentanedioate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution prepared from the compound B4 obtained in Step B of Example 1 (2.5 g-8 mmol), di-tert-butyl hydrochloride L-glutamate (2.36 g-8 mmol), EDCI (1.62 g-8 mmol), DIEA (1.32 ml-8 mmol) and HOBT (1.1 g-8 mmol) in 100 ml of anhydrous DMF is stirred for 72 hours at ambient temperature. The DMF is removed by distillation and then the residue is taken up in 100 ml of water and 100 ml of ethyl acetate. The organic phase is washed with 5% NaHCO3 solution and then with water, dried over Na2SO4 and evaporated to dryness. Purification by flash chromatography is carried out using a (90:10) dichloromethane/ethyl acetate mixture as eluant to yield the expected product in the form of a colourless oil.

Workup

  1. customThe DMF is removed by distillation
  2. washThe organic phase is washed with 5% NaHCO3 solution
  3. dry with materialwith water, dried over Na2SO4
  4. customevaporated to dryness
  5. customPurification by flash chromatography

Sources & evidence

ORD record
ord-9957a4209a1e499d8fea72086986f940
Source dataset
uspto-grants-2011_07
Patent number
US07981920B2

Reaction notes

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