Phosphorus oxide (P4O10) → Trimethyl(phosphooxy)silane

HRID 2233991Notes

Reaction equation

HRID 2233991 reaction equation
O=P12OP3(OP(OP(O3)(O1)=O)(=O)O2)=O.C[Si](C)(C)O[Si](C)(C)C.[Cl:24][C:25]1[N:30]=[C:29]([C:31]([NH2:33])=O)[CH:28]=[C:27]([N:34]2[CH2:39][CH2:38][CH:37]([NH:40][C:41]([C:43]3[NH:44][C:45]([CH3:50])=[C:46]([Cl:49])[C:47]=3[Cl:48])=[O:42])[CH2:36][CH2:35]2)[N:26]=1.[CH3:51][Si:52]([O:55][P:56](=[O:58])=[O:57])([CH3:54])[CH3:53]>C1(C)C=CC=CC=1>[CH3:51][Si:52]([O:55][P:56](=[O:58])=[O:57])([CH3:54])[CH3:53].[Cl:48][C:47]1[C:46]([Cl:49])=[C:45]([CH3:50])[NH:44][C:43]=1[C:41]([NH:40][CH:37]1[CH2:38][CH2:39][N:34]([C:27]2[CH:28]=[C:29]([C:31]#[N:33])[N:30]=[C:25]([Cl:24])[N:26]=2)[CH2:35][CH2:36]1)=[O:42]

Participants

7

Reactant 4

HCID 14812Phosphorus oxide (P4O10)HCID 24764HexamethyldisiloxaneHCID 16133246Trimethyl(phosphooxy)silane2×HCID 86608283HCID 86608283, compound

Product 2

HCID 16133246Trimethyl(phosphooxy)silaneHCID 86608334HCID 86608334, compound

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
80 °C

Procedure

A stock solution of trimethylsilyl polyphosphate (prepared according to Yokoyama, Masataka; Yoshida, Sayaka; Imamoto, Tsuneo. Synthesis, 1982, 7, 591-592) was prepared by combining P2O5 (10 g) and hexamethyldisiloxane (25 ml) in anhydrous toluene (50 ml) and heating the mixture at 80° C. until it became a clear solution (about 45 minutes). 2-Chloro-6-(4-{[(3,4-dichloro-5-methyl-1H-pyrrol-2-yl)carbonyl]amino}piperidin-1-yl)pyrimidine-4-carboxamide (Example 37, 2.1 g, 4.8 mmol) was treated with trimethylsilyl polyphosphate (80 ml), and the reaction was heated at 80° C. for 5 h, after which the reaction was about 50% complete. No further reaction was apparent after adding more trimethylsilyl polyphosphate and letting the reaction stir an additional 2.5 days. Upon cooling to room temperature, the reaction was concentrated under reduced pressure until most of the solvent was removed. The remaining liquid was triturated with EtOAc and water to form a brown precipitate, which was mostly the amide precursor. The mixture was filtered, and the filtrate was concentrated under reduced pressure to give the title compound as a yellow solid. About 20 mg was purified by preparatory HPLC, using a gradient of 35-75% acetonitrile/water (0.1% TFA), while the rest was carried on without further purification.

Workup

  1. customa clear solution (about 45 minutes)
  2. temperaturethe reaction was heated at 80° C. for 5 h
  3. customNo further reaction
  4. temperatureUpon cooling to room temperature
  5. concentrationthe reaction was concentrated under reduced pressure until most of the solvent
  6. customwas removed
  7. customThe remaining liquid was triturated with EtOAc and water
  8. customto form a brown precipitate, which
  9. filtrationThe mixture was filtered
  10. concentrationthe filtrate was concentrated under reduced pressure

Sources & evidence

ORD record
ord-e092c5545a2547b7acc424b9208f8e6f
Source dataset
uspto-grants-2010_05
Patent number
US07709503B2

Reaction notes

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