tert-Butyl hydroperoxide → HCID 11432643, compound

HRID 1176932Notes

Reaction equation

HRID 1176932 reaction equation
[OH:1][CH2:2][CH2:3][O:4][NH:5][C:6]([C:8]1[C:17]([NH:18][C:19]2[CH:24]=[CH:23][C:22]([Br:25])=[CH:21][C:20]=2[Cl:26])=[C:16]([F:27])[C:11]2[N:12]=[CH:13][N:14]([CH3:15])[C:10]=2[CH:9]=1)=[O:7].N1C=NN=N1.C(N(C(C)C)[P:37]([O:43]C(C)(C)C)[O:38]C(C)(C)C)(C)C.C([O:55]O)(C)(C)C>CN(C=O)C>[Br:25][C:22]1[CH:23]=[CH:24][C:19]([NH:18][C:17]2[C:8]([C:6]([NH:5][O:4][CH2:3][CH2:2][O:1][P:37](=[O:43])([OH:55])[OH:38])=[O:7])=[CH:9][C:10]3[N:14]([CH3:15])[CH:13]=[N:12][C:11]=3[C:16]=2[F:27])=[C:20]([Cl:26])[CH:21]=1

Participants

6

Reactant 4

HCID 6410tert-Butyl hydroperoxideHCID 853005Di-tert-butyl N,N-DiisopropylphosphoramiditeHCID 10127622SelumetinibHCID 178418441HCID 178418441, compound

Product 1

HCID 11432643HCID 11432643, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
-78 °C

Procedure

3.000 g of 6-(4-Bromo-2-chloro-phenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid (2-hydroxy-ethoxy)-amide, 660 mg of tetrazole and 2.80 mL of di-tertbutyl diisopropyl-phosphoramidite were dissolved/suspended in 30 mL of anhydrous DMF under an atmosphere of dry N2. The reaction mixture was stirred for about 3 hrs after which time the reaction was cooled to −78° C. and 2.50 mL of 70% tert-butyl hydrogen peroxide was added. The cooling bath was then taken away and the reaction was slowly warmed up to room temperature and reacted over night. The reaction was then partitioned between a solution of ethyl ether/ethyl acetate (5:1) and saturated aqueous NaHCO3. The organic layer was saved and successively washed with 10% aqueous sodium sulfite, 3 times with water and finally with brine. The resulting organic layer was dried over MgSO4, filtered and concentrated under vacuum. The residue was dissolved in 45 mL of a solution for about 2 hours after which time it was concentrated under vacuum and the resulting residue was stirred in methanol for about 1 hours. The off-white solid was collected via suction filtration, washed with methanol followed by ethyl ether and then air-dried to give 2.717 g of the desired product. 1H NMR (400 MHz, DMSO-d6) δ 11.94 (brs, 1H), 8.40 (s, 1H), 7.96 (brs, 1H), 7.75 (s, 1H), 7.60 (s, 1H), 7.25 (dd, 1H), 6.37 (dd, 1H), 4.02 (brs, 4H); 19F NMR (376 MHz, DMSO-d6)−132.9 (s, 1F).

Workup

  1. temperaturethe reaction was slowly warmed up to room temperature
  2. customreacted over night
  3. customThe reaction was then partitioned between a solution of ethyl ether/ethyl acetate (5:1) and saturated aqueous NaHCO3
  4. washsuccessively washed with 10% aqueous sodium sulfite, 3 times with water and finally with brine
  5. dry with materialThe resulting organic layer was dried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated under vacuum
  8. dissolutionThe residue was dissolved in 45 mL of a solution for about 2 hours after which time it
  9. concentrationwas concentrated under vacuum
  10. stirringthe resulting residue was stirred in methanol for about 1 hours
  11. filtrationThe off-white solid was collected via suction filtration
  12. washwashed with methanol
  13. customair-dried

Sources & evidence

ORD record
ord-59a0e93a7a024edeadb28340c9b6588b
Source dataset
uspto-grants-2010_11
Patent number
US07842816B2

Reaction notes

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