BOC-DAB(BOC)-OH DCHA

White crystalline powder

(2S)-3-{4-[2-Amino-6-({[2-(4-chlorophenyl)-1, 3-oxazol-4-yl]methyl}sulphanyl)-3, 5-dicyanopyridin-4-yl]phenoxy}propane-1, 2-diyl(2S, 2'S)-bis{2, 4-bis[(tert-butoxycarbonyl)amino]butanoate}An amount of 200 mg (0.375 mmol) of the compound from Example 8A was introduced in 15 ml of dichloromethane and admixed with 412 mg (0.824 mmol) of the A. Elongation of the Peptide on the Resin Each amino acid was added to the peptide sequence using standard Fmoc deprotection and coupling conditions. 22.7 g of Rink Amide MBHA resin was added to a 500 mL peptide reaction vessel. Each amino acid was added to the peptide-resin using the following steps: 1. Wash with 20% piperidine in DMF (250 mL×3 min) 2. Deprotect with 20% piperidine in DMF (250 mL×1 hour). 3. Wash with DMF (2×250 mL), DCM (2×250 mL), DMF (2×250 mL). 4. Dissolve amino acid (4 eq.) and 1-hydroxybenzotriazole (4 eq.) in DMF (250 mL). 5. Add amino acid solution to resin, and then add 1, 3-diisopropylcarbodiimide (4 eq.). 6. Shake resin with activated amino acid for 18 hours at 250 rpm on an orbital shaker, unless otherwise indicated. 7. Wash the resin with DMF (1×250 mL), DCM (2×250 mL), DMF (3×250 mL). 8. Check coupling using the quantitative ninhydrin test shown below. 9. Cleave a small amount of the peptide from the resin with 90% trifluoroacetic acid 5% triisopropylsilane, and 5% water. Check purity of peptide by analytical HPLC. The following is a list of the amino acids used in the synthesis: Amino Acid Amount Company Catalog No. 1. Pseudotripeptide*?** 47.2 g in house synthesis 2. Fmoc-L-Ile-OH 21.2 g Novabiochem 04-12-1024 3. Fmoc-L-Tyr(tBu)-OH 27.6 g Novabiochem 04-12-1037 4. Fmoc-L-Cys(Trt)-OH 35.1 g Novabiochem 04-12-1018 5. Fmoc-L-Leu-OH 21.2 g Novabiochem 04-12-1025 6. Fmoc-L-Gly-OH 17.8 g Novabiochem 04-12-1001 7. Fmoc-L-Tyr(3-Cl)-OH?? 26.3 g in house synthesis 8. Fmoc-L-Hyp(tBu)-OH 24.6 g Novabiochem 04-12-1078 9. Fmoc-L-Cys(Trt)-OH 35.1 g Novabiochem 04-12-1018 10. Fmoc-D-Glu-OH 25.5 g Novabiochem 04-13-1051 11. Fmoc-L-Tyr(tBu)-OH 27.6 g Novabiochem 04-12-1037 12. Boc-L-Dab(Boc)-OH.DCHA 30.0 g Bachem A-3480 *The pseudotripeptide was synthesized in house using the procedure shown below. 'The pseudotripeptide was allowed to couple over the weekend for three days. (Previous experience with the synthesis of EP2080 peptide has shown that this longer coupling time was required for the attachment of the first amino acid to the resin). **Typically the resin is capped with a solution of 5% acetic anhydride and 6% diisopropylethylamine in DMF after the first coupling. After the coupling of the amino acids is complete, the resin is washed with DMF (3 × 250 mL) and the capping solution (250 mL). The resin is shaken with the capping solution (250 mL) for 1 hour. ??Fmoc-Tyr(3-Cl)-OH was synthesized in house using the procedure shown below.; I. Cleavage, Cyclization and Purification Procedures i. Cleavage After the elongation of the peptide on the resin was complete, the resin was washed with DCM (3×250 mL). The resin was dried under reduced pressure at 22-25 C. for 18 hours. The weight of the dry peptide-resin (57.08 g) was determined. Approximately 15 mL/g (840 mL) of the following cleavage cocktail was added: 80% trifluoroacetic acid, 5% triisopropylsilane, 5% dodecanethiol, 5% dichloromethane, and 5% water. The peptide-resin was shaken for 1.25 hours at room temperature on an orbital shaker (250 rpm), and then filtered and washed with trifluoroacetic acid (2×100 mL). The filtrates were combined and poured into ether* (4 L) at 0 C. over 5 minutes to form a precipitate. The precipitate was filtered, washed with ether* (1 L), washed with acetonitrile (1 L), and dried under vacuum. 24.87 g. (73.3% purity by area, Analytical Method 2, 41.4% potency) (40% yield based on potency) *Isopropyl ether has been substituted for diethyl ether successfully on a 2 mmol scale.

Molecular Weight:499.7
Hydrogen Bond Donor Count:4
Hydrogen Bond Acceptor Count:7
Rotatable Bond Count:11
Exact Mass:499.36213629
Monoisotopic Mass:499.36213629
Topological Polar Surface Area:126
Heavy Atom Count:35
Complexity:525
Defined Atom Stereocenter Count:1
Covalently-Bonded Unit Count:2
Compound Is Canonicalized:Yes