Guanidinium → SF 6,6

HRID 2214418Notes

Reaction equation

HRID 2214418 reaction equation
[N+]([O-])(O)=O.CC1C=C(C)N(C(N)=N)N=1.[CH2:15]([CH2:28][CH2:29][N:30]=[C:31]([NH2:33])[NH2:32])[CH2:16][CH2:17][C:18]([NH:20][CH2:21][CH2:22][CH2:23][CH2:24][C:25](O)=O)=[O:19].CC(CCCCN)[C:36]([OH:38])=[O:37].C(OC(NCCCCCC(O)=O)=O)CCC.CC(CCCN)C(O)=O.C(OC(NCCCCC(O)=O)=O)CCC.NC(N)=[NH2+]>>[CH2:23]([CH2:22][CH2:21][NH:20][C:18]([CH2:17][CH2:16][CH2:15][CH2:28][CH2:29][N:30]=[C:31]([NH2:33])[NH2:32])=[O:19])[CH2:24][CH2:25][C:36]([OH:38])=[O:37]

Participants

8

Reactant 7

HCID 32838GuanidiniumHCID 126860SF 6,52×HCID 1981863,5-Dimethyl-1H-pyrazole-1-carboxamidine mononitrateHCID 13775857HCID 13775857, compoundHCID 19904999HCID 19904999, compoundHCID 21947175HCID 21947175, compoundHCID 21947176HCID 21947176, compound

Product 1

HCID 192346SF 6,6

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. customt produce the compound
  2. customCompounds AC-4 and AC-14 were prepared by stepwise synthesis either in solution or on a Merrifield resin
  3. customThe final compounds were purified on preparative RP-18 columns

Sources & evidence

ORD record
ord-36c895b63e2d4d5c9108d23f05f68d05
Source dataset
uspto-grants-2006_09
Patent number
US07109160B1

Reaction notes

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