Trimethylsilyl iodide → HCID 24856097, compound

HRID 227815Notes

Reaction equation

HRID 227815 reaction equation
[CH3:1][C:2]1[N:3]=[C:4]([C:7]2[C:16]3[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=3)[C:10]([NH:17][C:18]3[CH:55]=[CH:54][C:21]([O:22][C:23]4[C:28]([C:29]5[CH:34]=[CH:33][N:32]=[C:31]([NH:35][P:36](=[O:53])([O:45]CC6C=CC=CC=6)[O:37]CC6C=CC=CC=6)[N:30]=5)=[CH:27][CH:26]=[CH:25][N:24]=4)=[CH:20][CH:19]=3)=[N:9][N:8]=2)[S:5][CH:6]=1.C(#N)C.C(Cl)Cl.[I:62][Si](C)(C)C>CO>[IH:62].[IH:62].[CH3:1][C:2]1[N:3]=[C:4]([C:7]2[C:16]3[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=3)[C:10]([NH:17][C:18]3[CH:55]=[CH:54][C:21]([O:22][C:23]4[C:28]([C:29]5[CH:34]=[CH:33][N:32]=[C:31]([NH:35][P:36](=[O:37])([OH:45])[OH:53])[N:30]=5)=[CH:27][CH:26]=[CH:25][N:24]=4)=[CH:20][CH:19]=3)=[N:9][N:8]=2)[S:5][CH:6]=1

Participants

5

Reactant 3

HCID 85247Trimethylsilyl iodideHCID 21877088Acetonitrile methylene chlorideHCID 66731808HCID 66731808, compound

Product 1

HCID 24856097HCID 24856097, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a yellow slurry of N-(4-(3-(2-aminopyrimidin-4-yl)pyridin-2-yloxy)phenyl)-4-(4-methylthiazol-2-yl)phthalazin-1-amine (0.335 g, 0.664 mmol) and tetrabenzyl pyrophosphate (0.501 g, 0.930 mmol) in 6.6 mL THF under nitrogen at 0° C. was added sodium bis(trimethylsilyl)amide 1 M in THF (2.32 ml, 2.32 mmol) dropwise over 3 min to give a deep red solution. The reaction was quenched with sat'd aq. NaHCO3, and diluted with EtOAc. The organic layer was washed 3× with saturated aq. NaHCO3, 1× brine, dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo. The material was purified by silica gel chromatography, ISCO, 40 g, 50 min run, 0-60% 90/10 DCM/MeOH in DCM to give dibenzyl 4-(2-(4-(4-(4-methylthiazol-2-yl)phthalazin-1-ylamino)phenoxy)pyridin-3-yl)pyrimidin-2-ylphosphoramidate a yellow solid MS m/z=765 [M+H]+. Calc'd for C41H33N8O4PS: 764.8. Step 2. To a slightly cloudy mixture of dibenzyl 4-(2-(4-(4-(4-methylthiazol-2-yl)phthalazin-1-ylamino)phenoxy)pyridin-3-yl)pyrimidin-2-ylphosphoramidate (.086 g, 0.11 mmol) in 3 mL 5:1 ACN/DCM was added iodotrimethylsilane (0.16 ml, 1.1 mmol) dropwise via syringe at ambient temperature under nitrogen. After 5 min, 0.6 mL MeOH was added and the stir bar was removed. The reaction was concentrated in vacuo and suspended in DCM and filtered. The resulting orange solid was collected and dried in vacuo to provide

Workup

  1. customthe stir bar was removed
  2. concentrationThe reaction was concentrated in vacuo
  3. filtrationfiltered
  4. customThe resulting orange solid was collected
  5. customdried in vacuo
  6. customto provide

Sources & evidence

ORD record
ord-9aefd4d372bd4acba0654290ee17b167
Source dataset
uspto-grants-2009_07
Patent number
US07560551B2

Reaction notes

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