* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
With potassium carbonate; In hydrogenchloride; water;
A. 7-Guanidinoheptanoic acid is prepared essentially by the method of Miller, et al, Synthesis, 777 (1986), which is incorporated herein by reference. 0.50 g of 7-aminoheptanoic acid is dissolved in a solution of 0.475 g of potassium carbonate in 3.5 ml of water. 0.427 g of <strong>[1184-90-3]aminoiminomethanesulfonic acid</strong> is added portionwise over 10 minutes and the mixture stirred at room temperature for 24 hours. The resulting solid is collected by filtration. The guanidine is dissolved in diluted hydrochloric acid and the solution evaporated in vacuo. Two portions of 2-propanol are evaporated from the residue to give 7-guanidinoheptanoic acid hydrochloride.
The carboxylic acid of compound 533 (obtainable from SALOR, catalogue number S532649) is activated with one equivalent of EDC and 1.2 equivalents of NHS in DMSO for 4h at 30 0C prior to addition of ten equivalents of 7-aminoheptanoic acid and triethylamine. The reaction is stirred overnight at 30 C, to yield 533-aminoheptanoic acid. The product is purified by HPLC and analysed by mass-spectrometry.
Figure 1 shows possible building-block reagents, starting from which the compounds of the inventions may be synthesised. The carboxylic acid of compound 428 (obtainable from SIGMA, catalogue number 15634) was activated with one equivalent of EDC and 1.2 equivalents of NHS in DMSO for 4h at 30 0C prior to addition of ten equivalents of 7-aminoheptanoic acid and triethylamine. The reaction was stirred overnight at 30 C, to EPO <DP n="44"/>yield 428-aminoheptanoic acid. The product was purified by HPLC (see Example 21, General Methods) and analysed by mass-spectrometry.
In one preparation, 428-aminoheptanoic acid: 10 mumol of 428 were stirred with 8 mumol of N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide (EDC) and 10 mumol of N- hydroxysuccinimide (NHS) in 50 mul of DMSO for 3 hours at 30 0C followed by addition of 20 mumol of 7-aminoheptanoic acid (Bachem) in 100 mul of 1 M NaHCO3, pH 9. The reaction was allowed to stir overnight at 30 0C. After quenching of remaining reagents with excess of Trizma base the reaction was purified by HPLC and characterized by mass spectrometry.
With sodium hydrogencarbonate; In water; acetonitrile; for 4h;
To a solution of BCN-OSu derivative 51 in MeCN (5 mL) were added 7-aminoheptanoic acid 50 (145 mg, 1.0 mmol) in 0.1 M aqueous NaHCO3 (30 mL) and MeCN (25 mL). The mixture was stirred for 4 h and partially concentrated. Aqueous saturated NH4C1 (30 mL) was added and after extraction with DCM (2 x 30 mL), the combined organics were dried (Na2SO4) and concentrated. Product 52 was used in the step without furtherpurification. ‘H NIVIR (400 IVIHz, CDC13) (ppm) 4.68 (bs, 1H), 4.14 (d, J 7.9 Hz, 2H),3.17 (dd, J= 12.8, 6.3 Hz, 2H), 2.35 (t, J= 7.5 Hz, 2H), 2.32-2.09 (m, 6H), 1.70-1.25 (m, 1 1H), 0.94 (t, J 9.7 Hz, 2H).
Chemistry
Pharmaceutical Intermediates
Inhibitors/Agonists
Material Science
For Research Only
120K+ Compounds
Competitive Price
1-2 Day Shipping
