Dicyclohexylcarbodiimide → SF 6,5

HRID 2214417Notes

Reaction equation

HRID 2214417 reaction equation
C[CH:2]([CH2:6][CH2:7][CH2:8][NH2:9])[C:3]([OH:5])=[O:4].C(OC([NH:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][C:23](O)=[O:24])=O)CCC.C1([N:32]=[C:33]=[N:34]C2CCCCC2)CCCCC1.[OH:41][C:42]1[C:50]2[N:49]=NN[C:46]=2[CH:45]=[CH:44][CH:43]=1>>[CH2:45]([CH2:46][CH2:50][N:49]=[C:33]([NH2:34])[NH2:32])[CH2:44][CH2:43][C:42]([NH:9][CH2:8][CH2:7][CH2:6][CH2:2][C:3]([OH:5])=[O:4])=[O:41].[CH2:20]([CH2:19][CH2:18][NH2:17])[CH2:21][CH2:22][C:23]([NH:9][CH2:8][CH2:7][CH2:6][CH2:2][C:3]([OH:5])=[O:4])=[O:24]

Participants

6

Reactant 4

HCID 10868DicyclohexylcarbodiimideHCID 19904999HCID 19904999, compoundHCID 21947175HCID 21947175, compoundHCID 178418300HCID 178418300, compound

Product 2

HCID 126860SF 6,5HCID 1303275-[(6-Amino-1-hydroxyhexylidene)amino]pentanoic acid

Procedure

In Greenspoon et al., the design and preparation of nonpeptide analogues of RGD are described as follows. Compounds SF-6,5 and SFN-70 were prepared by coupling of methyl-5-aminovaleric acid with N-(butyloxycarbonyl)-6-aminohexanoic acid. The reaction was carried out using the 1,3-dicyclohexylcarbodiimide and 1 hydroxybenzotriazole in tetrahydroduran procedure. The butyloxycarbonyl protecting group was then removed by 50% trifluoroacetic acid in dichloromethane. Removal of the methyl ester protecting group was carried out with sodium hydroxide at pH 9.5, yielding SFN-70. The amine was converted to guanidium using 3,5-dimethylpyrazole-1-carboxamidine nitrate at pH 9.5 t produce the compound designated SF-6,5. Compound SF-6,6 was prepared from methyl-6-aminohexanoic acid and N-(butyloxycarbonyl)-6-aminohexanoic acid under the same conditions as used for SF-6,5. GK-5,5 was prepared from methyl-5-aminovaleric acid and N-(butyloxycarbonyl)-5-aminovaleric acid. Compounds AC-4 and AC-14 were prepared by stepwise synthesis either in solution or on a Merrifield resin, followed by deprotection and conversion of the amine to the guanidinium by the above-described methods. The final compounds were purified on preparative RP-18 columns and were judged pure by thin-layer chromatography (single spot) and 1H NMR spectroscopy. Compounds were characterized by 1H NMR and FAB-MS spectroscopy. The structures deduced from spectroscopy were consistent with the assigned structure. (Table 1). Table 1 shows a schematic presentation of the RGD-NH2 peptide and the corresponding non-peptide surrogates. Note that the distance between positions a and b is 11 atoms.

Workup

  1. customIn Greenspoon et al., the design and preparation of nonpeptide analogues of RGD
  2. customThe butyloxycarbonyl protecting group was then removed by 50% trifluoroacetic acid in dichloromethane
  3. customRemoval of the methyl ester protecting group

Sources & evidence

ORD record
ord-c08f9821a4da4013b968da1f69d78e19
Source dataset
uspto-grants-2006_09
Patent number
US07109160B1

Reaction notes

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