Methanol → (2-{4-[(2,4-Diamino-pteridin-6-ylmethyl)-methyl-amino]-benzoylamino}-propyl)-phosphonic acid

HRID 2378848Notes

Reaction equation

C([O:3][P:4]([CH2:9][CH:10]([NH:12][C:13](=[O:35])[C:14]1[CH:19]=[CH:18][C:17]([N:20]([CH2:22][C:23]2[N:24]=[C:25]3[C:30](=[N:31][CH:32]=2)[N:29]=[C:28]([NH2:33])[N:27]=[C:26]3[NH2:34])[CH3:21])=[CH:16][CH:15]=1)[CH3:11])(=[O:8])[O:5]CC)C.C[Si](Br)(C)C.O.CO>CN(C=O)C>[NH2:33][C:28]1[N:27]=[C:26]([NH2:34])[C:25]2[C:30](=[N:31][CH:32]=[C:23]([CH2:22][N:20]([CH3:21])[C:17]3[CH:16]=[CH:15][C:14]([C:13]([NH:12][CH:10]([CH3:11])[CH2:9][P:4](=[O:3])([OH:8])[OH:5])=[O:35])=[CH:19][CH:18]=3)[N:24]=2)[N:29]=1

Participants

Conditions

Temperature: 70 °C

Procedure

To a solution of crude (2-{4-[(2,4-diamino-pteridin-6-ylmethyl)-methyl-amino]-benzoylamino}-propyl)-phosphonic acid diethyl ester post silica column chromatography (32.2 mg, 66.2 μmol) in dry DMF (0.50 mL) was added TMSBr (68.0 μL, 529.6 μmol) at ambient temperature. The solution was then heated at 70° C. for 1.0 hour, when LCMS analysis demonstrated the reaction to be complete. The reaction mixture was allowed to cool to room temperature, and water (60 μL) and methanol (60 μL) were added. The crude reaction mixture was purified by RP HPLC on C18 column using H2O/acetonitrile (2-95%) to provide 11.2 mg (38%) of the desired compound as a yellow solid. 1H NMR (300 MHz, DMSO-d6) δ 1.50 (m, 2H), 1.61 (m, 2H), 3.22 (s, 3H), 3.25-3.40 (m, 2H), 4.84 (s, 2H), 6.80 (d, 2H, J=9 Hz), 7.69 (d, 2H, J=9 Hz), 8.20 (br s, 1H), 8.69 (s, 1H). 31P (121.4 MHz, DMSO-d6) δ 26.3. MS (m/z) 447.3 [M−H]−.

Workup

customthe reaction
temperatureto cool to room temperature
customThe crude reaction mixture
customwas purified by RP HPLC on C18 column

Sources & evidence

ORD record: ord-b963ae41fd5f4ba3ba1553dd9430aee8
Source dataset: uspto-grants-2008_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07470724B2

Reaction notes

Loading…