Cidofovir → Hpmpc deea

HRID 1787534

Reaction equation

HRID 1787534 reaction equation
[CH:1]1[C:7]([NH2:8])=[N:6][C:4](=[O:5])[N:3]([CH2:9][C@H:10]([O:13][CH2:14][P:15]([OH:18])([OH:17])=[O:16])[CH2:11][OH:12])[CH:2]=1.[CH3:19][CH2:20][N:21]([CH:25]([CH3:27])C)[CH:22](C)[CH3:23]>CN(C=O)C>[CH:1]1[C:7]([NH2:8])=[N:6][C:4](=[O:5])[N:3]([CH2:9][C@H:10]([O:13][CH2:14][P:15]([OH:18])([OH:17])=[O:16])[CH2:11][OH:12])[CH:2]=1.[CH3:19][CH2:20][N:21]([CH2:25][CH2:27][OH:5])[CH2:22][CH3:23]

Participants

4

Reactant 2

HCID 60613CidofovirHCID 81531Diisopropylethylamine

Product 1

HCID 131727368Hpmpc deea

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To prepare compound 5 of FIG. 2, 135 mg (0.428 mmol) cidofovir was exposed to 135 mg (1.04 mmol) DIEA and dissolved in 4 mL DMF. A HPMPC-DEEA salt was obtained after solvent was removed under vacuum. 650 mg (1.8 mmol) dipeptide (t-BOC-Val-Ser-t-butyl described above) was added to a reaction flask containing the HPMPC-DIEA salt and 4 mL dry DMF. 660 mg (1.27 mmol) PyBOP and 425 μL (2.44 mmol) DIEA were added, and the reaction took place stirring under N2 (g) at 40° C. for 1 h. An additional 330 mg (0.635 mmol) PyBOP was added and left for 3 additional hours. Solvents were removed under vacuum, and a silica gel column chromatography purification was performed [eluent; CH2Cl2:acetone:methanol, 20:10:1.]. Solvent was removed and deprotection of the t-BOC and t-butoxy groups was performed in 4 mL of CH2Cl2 in the presence of 2 mL of 99% TFA for 3 h at room temperature. Solvents were removed under vacuum and ether was added to precipitate the final compound, 5, which was filtered by methanol on a funnel containing a silica gel layer. Preparative HPLC purification on a C-18 column (5 μm, 100 Å, 21.4×250 mm by Varian) was obtained using a mobile phase containing 0.1 M TEA and 3.5% acetonitrile at pH 6.7 adjusted with acetic acid. A fraction of the sample was purified by preparative HPLC methods and evaluated by NMR and HR-MS techniques. 1H NMR (CD3OD): δ 0.94 (6H, m), 2.10 (1H, m), 2.94-5.73 (10H, m), 5.73 (1H, m), 7.40 (1H, m). 31P NMR (CD3OD): δ 14.3 and 15.6 (1P, 2s). Exact mass (C16H26N5O8P); 447.1519 m/z.

Sources & evidence

ORD record
ord-ed3ede8042944099a2819d35f0a63185
Source dataset
uspto-grants-2009_03
Patent number
US07511051B2

Linked notes

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