Dicyclohexylcarbodiimide → 2-N-(4-Methoxy-2,3,6-trimethyl-benzenesulfonyl)-4-N-(beta-D-galactopyranosyl)-L-asparaginyl-4-amidino-D-phenylalanine-piperidide hydrochloride

HRID 743674

Reaction equation

HRID 743674 reaction equation
[ClH:1].[CH3:2][O:3][C:4]1[CH:9]=[C:8]([CH3:10])[C:7]([S:11]([NH:14][C@H:15]([C:20]([NH:22][C@@H:23]([C:34]([N:36]2[CH2:41][CH2:40][CH2:39][CH2:38][CH2:37]2)=[O:35])[CH2:24][C:25]2[CH:30]=[CH:29][C:28]([C:31](=[NH:33])[NH2:32])=[CH:27][CH:26]=2)=[O:21])[CH2:16][C:17](=[O:19])[NH2:18])(=[O:13])=[O:12])=[C:6]([CH3:42])[C:5]=1[CH3:43].C1C=CC2N(O)N=NC=2C=1.C1CCC(N=C=NC2CCCCC2)CC1.[C@@H:69]1(N)[O:77][C@H:76]([CH2:78][OH:79])[C@H:74]([OH:75])[C@H:72]([OH:73])[C@H:70]1[OH:71]>CN(C=O)C.ClCCl>[ClH:1].[CH3:2][O:3][C:4]1[CH:9]=[C:8]([CH3:10])[C:7]([S:11]([NH:14][C@H:15]([C:20]([NH:22][C@@H:23]([C:34]([N:36]2[CH2:41][CH2:40][CH2:39][CH2:38][CH2:37]2)=[O:35])[CH2:24][C:25]2[CH:26]=[CH:27][C:28]([C:31](=[NH:32])[NH2:33])=[CH:29][CH:30]=2)=[O:21])[CH2:16][C:17](=[O:19])[NH:18][C@@H:69]2[O:77][C@H:76]([CH2:78][OH:79])[C@H:74]([OH:75])[C@H:72]([OH:73])[C@H:70]2[OH:71])(=[O:13])=[O:12])=[C:6]([CH3:42])[C:5]=1[CH3:43]

Participants

7

Reactant 4

HCID 10868DicyclohexylcarbodiimideHCID 757711-HydroxybenzotriazoleHCID 11095207(2R,3R,4S,5R,6R)-2-Amino-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triolHCID 228655222-N-(4-Methoxy-2,3,6-trimethyl-benzenesulfonyl)-L-asparaginyl-4-amidino-D-phenylalanine-piperidide hydrochloride

Product 1

HCID 867498292-N-(4-Methoxy-2,3,6-trimethyl-benzenesulfonyl)-4-N-(beta-D-galactopyranosyl)-L-asparaginyl-4-amidino-D-phenylalanine-piperidide hydrochloride

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

2-N-(4-Methoxy-2,3,6-trimethyl-benzenesulfonyl)-L-asparaginyl-4-amidino-D-phenylalanine-piperidide hydrochloride (1.0 g), HOBt (0.23 g) and DCCI (0.37 g) were dissolved in DMF and dichloromethane 1:1 (50 mL) and, after 0.5 h of stirring, β-D-galactopyranosyl-amine (1.0 g) was added. The reaction mixture was stirred for 48 h at room temperature and then filtered and concentrated by evaporation in vacuo. The residue was dissolved in ethyl acetate and washed with water. The crude product was purified by column chromatography on silica gel with chloroform/methanol 5:1. Yield: 1.2 g. TLC analysis: Rf=0.73 (chloroform/methanol 3:1). Barium oxide (0.25 g) was added to a solution of the intermediate compound (1.2 g) in chloroform/methanol 2:1 (100 mL), and the mixture was stirred for 2 h and then filtered. The flitrate was neutralized with methanolic HCl and concentrated by evaporation in vacuo. The residue was purified by column chromatography (Sephadex LH 20). Yield: 1.0 g. TLC analysis: Rf=0.042 (chloroform/methanol 3:1). [α]D +19.3° (c=1 in methanol). M.p. 186°-190° C.

Workup

  1. filtrationfiltered
  2. concentrationconcentrated by evaporation in vacuo
  3. dissolutionThe residue was dissolved in ethyl acetate
  4. washwashed with water
  5. customThe crude product was purified by column chromatography on silica gel with chloroform/methanol 5:1
  6. additionBarium oxide (0.25 g) was added to a solution of the intermediate compound (1.2 g) in chloroform/methanol 2:1 (100 mL)
  7. stirringthe mixture was stirred for 2 h
  8. filtrationfiltered
  9. concentrationconcentrated by evaporation in vacuo
  10. customThe residue was purified by column chromatography (Sephadex LH 20)

Sources & evidence

ORD record
ord-13a90241968442bca6897c65371ce9a1
Source dataset
uspto-grants-1996_09
Patent number
US05556941

Linked notes

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