Bromotrimethylsilane → (4-((4-amino-6-(2-methoxyethoxy)-2-oxo-2,3-dihydro-1H-imidazo[4,5-c]pyridin-1-yl)methyl)benzyl)phosphonic acid

HRID 629939Notes

Reaction equation

HRID 629939 reaction equation
[NH2:1][C:2]1[C:7]2[NH:8][C:9](=[O:27])[N:10]([CH2:11][C:12]3[CH:26]=[CH:25][C:15]([CH2:16][P:17](=[O:24])([O:21]CC)[O:18]CC)=[CH:14][CH:13]=3)[C:6]=2[CH:5]=[C:4]([O:28][CH2:29][CH2:30][O:31][CH3:32])[N:3]=1.C[Si](Br)(C)C>C(Cl)Cl>[NH2:1][C:2]1[C:7]2[NH:8][C:9](=[O:27])[N:10]([CH2:11][C:12]3[CH:26]=[CH:25][C:15]([CH2:16][P:17](=[O:18])([OH:21])[OH:24])=[CH:14][CH:13]=3)[C:6]=2[CH:5]=[C:4]([O:28][CH2:29][CH2:30][O:31][CH3:32])[N:3]=1

Participants

4

Reactant 2

HCID 76113BromotrimethylsilaneHCID 86667765diethyl 4-((4-amino-6-(2-methoxyethoxy)-2-oxo-2,3-dihydro-1H-imidazo[4,5-c]pyridin-1-yl)methyl)benzylphosphonate

Product 1

HCID 56932998(4-((4-amino-6-(2-methoxyethoxy)-2-oxo-2,3-dihydro-1H-imidazo[4,5-c]pyridin-1-yl)methyl)benzyl)phosphonic acid

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
22 °C

Procedure

To a solution of diethyl 4-((4-amino-6-(2-methoxyethoxy)-2-oxo-2,3-dihydro-1H-imidazo[4,5-c]pyridin-1-yl)methyl)benzylphosphonate (1 equiv.) in CH2Cl2 (0.10 M) at 0° C. was slowly added trimethylsilyl bromide (10 equiv.). After 1 h the ice-bath was removed and the reaction mixture was allowed to stir at 22° C. for 18 h. At this point the volatiles were removed in vacuo and the resulting residue was purified by Reverse Phase-HPLC using a 20-90% 0.5 mM NH4OAc (in MeCN) to 10 mM NH4OAc (in water) gradient to deliver the title compound (41%) as a solid.

Workup

  1. customat 0° C.
  2. customAfter 1 h the ice-bath was removed
  3. customAt this point the volatiles were removed in vacuo
  4. customthe resulting residue was purified by Reverse Phase-HPLC

Sources & evidence

ORD record
ord-26ea2beda09a4810b590d2752b3c03c6
Source dataset
uspto-grants-2016_04
Patent number
US09315530B2

Reaction notes

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