Bromotrimethylsilane → N-(4-Amino-4-deoxy-N-methylpteroyl)-3-aminoethanephosphonic acid

HRID 2378846Notes

Reaction equation

HRID 2378846 reaction equation
C([O:3][P:4]([CH2:9][CH2:10][NH:11][C:12](=[O:34])[C:13]1[CH:18]=[CH:17][C:16]([N:19]([CH2:21][C:22]2[N:23]=[C:24]3[C:29](=[N:30][CH:31]=2)[N:28]=[C:27]([NH2:32])[N:26]=[C:25]3[NH2:33])[CH3:20])=[CH:15][CH:14]=1)(=[O:8])[O:5]CC)C.C[Si](Br)(C)C>CN(C=O)C>[NH2:32][C:27]1[N:26]=[C:25]([NH2:33])[C:24]2[C:29](=[N:30][CH:31]=[C:22]([CH2:21][N:19]([CH3:20])[C:16]3[CH:15]=[CH:14][C:13]([C:12]([NH:11][CH2:10][CH2:9][P:4](=[O:3])([OH:8])[OH:5])=[O:34])=[CH:18][CH:17]=3)[N:23]=2)[N:28]=1

Participants

4

Reactant 2

HCID 76113BromotrimethylsilaneHCID 57496978HCID 57496978, compound

Product 1

HCID 481660N-(4-Amino-4-deoxy-N-methylpteroyl)-3-aminoethanephosphonic acidYield 53%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
70 °C

Procedure

To a solution of crude (2-{4-[(2,4-diamino-pteridin-6-ylmethyl)-methyl-amino]-benzoylamino}-ethyl)-phosphonic acid diethyl ester post silica column chromatography (61 mg, 125 μmol) in dry DMF (1.00 mL) was added TMSBr (129.0 μL, 999.2 μmol) at ambient temperature. The solution was then heated at 70° C. for 5.5 hours, when LCMS analysis demonstrated the reaction to be 90% complete. The reaction mixture was allowed to cool to room temperature and stirred for an additional 12 hours. The reaction was worked up by removal of the solvent in vacuo and dissolving the residue in DMF/H2O (800 μL, 1:1) and 1N aqueous NaOH (15 μL). The product was purified by RP HPLC on C18 column using H2O/acetonitrile (2-95%) to provide 29 mg (53%) of the desired compound as a yellow solid. 1H NMR (300 MHz, DMSO-d6) δ 1.67-1.85 (m, 2H), 3.19 (s, 3H), 3.25-3.40 (m, 2H), 4.76 (s, 2H), 6.71 (br s, 2H), 5.80 (d, 2H, J=9 Hz), 7.64 (d, 2H, J=9 Hz), 7.73 (br s, 2H), 8.15 (br s, 1H), 8.56 (s, 1H). 31P (121.4 MHz, DMSO-d6) δ 23.0. MS (m/z) 431.3 [M−H]−.

Workup

  1. customthe reaction
  2. temperatureto cool to room temperature
  3. customThe reaction was worked up by removal of the solvent in vacuo
  4. dissolutiondissolving the residue in DMF/H2O (800 μL, 1:1)
  5. customThe product was purified by RP HPLC on C18 column

Sources & evidence

ORD record
ord-70cf8c6767774ed08267a2a6a004a505
Source dataset
uspto-grants-2008_12
Patent number
US07470724B2

Reaction notes

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