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

HRID 272222Notes

Reaction equation

HRID 272222 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-4755b98114b54922b214d9f5a993ff04
Source dataset
uspto-grants-2008_11
Patent number
US07452901B2

Reaction notes

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