tert-Butyl hydroperoxide → Phosphoric acid mono-(2-{[7-(4-bromo-2-chlorophenylamino)-8-chloro-imidazo[1,2-a]pyridine-6-carbonyl]-aminooxy}-ethyl) ester

HRID 494730

반응식

HRID 494730 반응식
[OH:1][CH2:2][CH2:3][O:4][NH:5][C:6]([C:8]1[C:9]([NH:18][C:19]2[CH:24]=[CH:23][C:22]([Br:25])=[CH:21][C:20]=2[Cl:26])=[C:10]([Cl:17])[C:11]2[N:12]([CH:14]=[CH:15][N:16]=2)[CH:13]=1)=[O:7].N1C=NN=N1.C(N(C(C)C)[P:36]([O:42]C(C)(C)C)[O:37]C(C)(C)C)(C)C.C([O:54]O)(C)(C)C>CN(C=O)C>[Br:25][C:22]1[CH:23]=[CH:24][C:19]([NH:18][C:9]2[C:8]([C:6]([NH:5][O:4][CH2:3][CH2:2][O:1][P:36](=[O:42])([OH:54])[OH:37])=[O:7])=[CH:13][N:12]3[CH:14]=[CH:15][N:16]=[C:11]3[C:10]=2[Cl:17])=[C:20]([Cl:26])[CH:21]=1

참가 물질

6

반응물 4

HCID 6410tert-Butyl hydroperoxideHCID 853005Di-tert-butyl N,N-DiisopropylphosphoramiditeHCID 117195477-(4-Bromo-2-chlorophenylamino)-8-chloroimidazo[1,2-a]pyridine-6-carboxylic acid (2-hydroxyethoxy)-amideHCID 178418441HCID 178418441, 화합물

생성물 1

HCID 58760505Phosphoric acid mono-(2-{[7-(4-bromo-2-chlorophenylamino)-8-chloro-imidazo[1,2-a]pyridine-6-carbonyl]-aminooxy}-ethyl) ester

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

반응 조건

온도
-78 °C

실험 절차

7-(4-bromo-2-chlorophenylamino)-8-chloroimidazo[1,2-a]pyridine-6-carboxylic acid (2-hydroxyethoxy)-amide (33a) (100 mg, 0.234 mmol), tetrazole (23 mg, 0.327 mmol) and di-tert-butyl diisopropylphosphoramidite (0.096 mL, 0.304 mmol) were dissolved/suspended in 30 mL of anhydrous DMF under an atmosphere of dry N2. The reaction mixture was stirred for about 3 hours, after which time the reaction was cooled to −78° C. and tert-butyl hydrogen peroxide (0.100 mL of 70% solution in water) 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 mixture 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 3 mL of a solution of TFA/DCM (2:1) under an atmosphere of dry N2. The reaction was stirred at room temperature for about 2 hours after which time it was concentrated under vacuum and the resulting residue was stirred in methanol for about 1 hour. The off-white solid was collected via suction filtration, washed with methanol followed by ethyl ether and then air-dried to give the desired compound (74).

후처리

  1. temperaturethe reaction was slowly warmed up to room temperature
  2. customreacted over night
  3. customThe reaction mixture 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 3 mL of a solution of TFA/DCM (2:1) under an atmosphere of dry N2
  9. stirringThe reaction was stirred at room temperature for about 2 hours after which time it
  10. concentrationwas concentrated under vacuum
  11. stirringthe resulting residue was stirred in methanol for about 1 hour
  12. filtrationThe off-white solid was collected via suction filtration
  13. washwashed with methanol
  14. customair-dried

출처 및 근거

ORD 기록
ord-70ddc00b8abe44eb9ba70ce46d45ab07
출처 데이터셋
uspto-grants-2009_05
특허 번호
US07538120B2

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