Bromotrimethylsilane → HCID 56933057, compound

HRID 629947Notes

Reaction equation

HRID 629947 reaction equation
[NH2:1][C:2]1[N:7]=[C:6]([CH3:8])[C:5]([CH2:9][C:10]2[CH:32]=[CH:31][C:13]([O:14][CH2:15][CH2:16][O:17][CH2:18][CH2:19][C:20]([P:23](=[O:30])([O:27]CC)[O:24]CC)([F:22])[F:21])=[CH:12][C:11]=2[O:33][CH3:34])=[C:4]([NH:35][CH2:36][CH2:37][CH2:38][CH2:39][CH3:40])[N:3]=1.C[Si](Br)(C)C>C(Cl)Cl>[NH2:1][C:2]1[N:7]=[C:6]([CH3:8])[C:5]([CH2:9][C:10]2[CH:32]=[CH:31][C:13]([O:14][CH2:15][CH2:16][O:17][CH2:18][CH2:19][C:20]([P:23](=[O:24])([OH:27])[OH:30])([F:22])[F:21])=[CH:12][C:11]=2[O:33][CH3:34])=[C:4]([NH:35][CH2:36][CH2:37][CH2:38][CH2:39][CH3:40])[N:3]=1

Participants

4

Reactant 2

HCID 76113BromotrimethylsilaneHCID 86667773HCID 86667773, compound

Product 1

HCID 56933057HCID 56933057, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
22 °C

Procedure

To a solution of diethyl (3-(2-(4-((2-amino-4-methyl-6-(pentylamino)pyrimidin-5-yl)methyl)-3-methoxyphenoxy)ethoxy)-1,1-difluoropropyl)phosphonate (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 (70%) 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-2abf52f264ae41dab619d63c17038bce
Source dataset
uspto-grants-2016_04
Patent number
US09315530B2

Reaction notes

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