4-Methylmorpholine → HCID 15799499, compound

HATU (66.5 mg, 0.175 mmol, 0.7 mole eq.) in NMP (0.5 mL) were added to a solution of N,N-bis[3-(Fmoc-amino)propyl]glycine potassium sulphate (115.5 mg, 0.15 mmol, 0.6 mole eq.) and NMM (33.05 μL, 0.3 mmol, 1.2 mole eq.) in NMP (1 mL). This solution was dropwise added in 5 min to a suspension of r-BHD (Compound 1) (100 mg, 0.25 mmol) in NMP (5 mL) containing NMM (27.5 μL, 0.25 mmol, 1 mole eq.). The reaction mixture was stirred at room temp. monitoring the reaction by RP-HPLC (eluent: from 30% to 100% of B in 20 mim; tR=13.4 min). After 2.5 h, Compound 1 (57.7 mg, 0.08 mmol, 0.3 mole eq.) was added again to the reaction mixture. After 2.5 h the reaction was stopped and the solvent evaporated under reduced pressure. The yellow-orange oil was suspended in water at 0° C. under stirring obtaining a white precipitate that was purified by RP-CC (LiChroprep RP-8, 40-63 μm; 170×20 mm; eluent: CH3CN/H2O/HCl=50:50:0.1, 1 mL/min) giving Compound 2 (130 mg; 55% yield). The Fmoc-protected bis-amino derivative (Compound 2) appeared to be pure by T.L.C. inspection (CH3CN/H2O/HCl=50:50:0.1). 1HNMR (200 MHz, DMSO): δ 9.63 (br s, 1H), 8.64 (br s, 3H), 7.87 (d, 4H), 7.65 (d, 4H), 7.43-7.27 (m, 8H), 6.41 (d, 2H), 4.31-4.14 (m, 8H), 3.85 (s, 2H), 3.14-3.03 (m, 11H), 2.82-2.76 (m, 4H), 2.6 (d, 2H), 1.76-1.25 (m, 20H) ESI-MS (m/e): calculated [M+H]+ 944.5, found 944.5.

1. customthe reaction by RP-HPLC (eluent: from 30% to 100% of B in 20 mim; tR=13.4 min)
2. waitAfter 2.5 h the reaction was stopped
3. customthe solvent evaporated under reduced pressure
4. customwas suspended in water at 0° C.
5. stirringunder stirring
6. customobtaining a white precipitate that
7. customwas purified by RP-CC (LiChroprep RP-8, 40-63 μm; 170×20 mm; eluent: CH3CN/H2O/HCl=50:50:0.1, 1 mL/min)

ORD record

ord-9d16e8d22c6f4e90bae6c737810388d0

Source dataset

uspto-grants-2010_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07816388B2