Hydrogen Peroxide → Di-tert-butyl 3-(4-(2-(4-(4-phenylphthalazin-1-ylamino)phenoxy)pyridin-3-yl)pyrimidin-2-ylamino)propyl phosphate

HRID 227791ノート

反応式

HRID 227791 の反応式
[C:1]1([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:41]=[CH:40][C:21]([O:22][C:23]4[C:28]([C:29]5[CH:34]=[CH:33][N:32]=[C:31]([NH:35][CH2:36][CH2:37][CH2:38][OH:39])[N:30]=5)=[CH:27][CH:26]=[CH:25][N:24]=4)=[CH:20][CH:19]=3)=[N:9][N:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.CC(N(C)C)=[O:44].C(N(CC)[P:51]([O:57][C:58]([CH3:61])([CH3:60])[CH3:59])[O:52][C:53]([CH3:56])([CH3:55])[CH3:54])C.N1C=NN=N1.OO.O>>[P:51]([O:39][CH2:38][CH2:37][CH2:36][NH:35][C:31]1[N:30]=[C:29]([C:28]2[C:23]([O:22][C:21]3[CH:20]=[CH:19][C:18]([NH:17][C:10]4[C:11]5[C:16](=[CH:15][CH:14]=[CH:13][CH:12]=5)[C:7]([C:1]5[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=5)=[N:8][N:9]=4)=[CH:41][CH:40]=3)=[N:24][CH:25]=[CH:26][CH:27]=2)[CH:34]=[CH:33][N:32]=1)([O:52][C:53]([CH3:54])([CH3:55])[CH3:56])([O:57][C:58]([CH3:59])([CH3:60])[CH3:61])=[O:44]

参加物

7

反応物 6

HCID 784Hydrogen PeroxideHCID 962WaterHCID 31374DimethylacetamideHCID 4251849Di-tert-butyl diethylphosphoramiditeHCID 667319743-(4-(2-(4-(4-Phenylphthalazin-1-ylamino)phenoxy)pyridin-3-yl)pyrimidin-2-ylamino)propan-1-olHCID 178418441HCID 178418441、化合物

生成物 1

HCID 66731722Di-tert-butyl 3-(4-(2-(4-(4-phenylphthalazin-1-ylamino)phenoxy)pyridin-3-yl)pyrimidin-2-ylamino)propyl phosphate

実験手順

A 15 mL RBF under nitrogen was charged with 3-(4-(2-(4-(4-phenylphthalazin-1-ylamino)phenoxy)pyridin-3-yl)pyrimidin-2-ylamino)propan-1-ol (130 mg, 0.24 mmol) in DMA (1.2 mL, 0.24 mmol). To this was added di-tert-butyl diethylphosphoramidite (0.14 mL, 0.57 mmol) and 1-H-tetrazole (1.1 mL, 0.49 mmol). The reaction mixture was stirred at RT for 2 hrs, then cooled to −5° C. and hydrogen peroxide −30 wt. % in water (0.05 mL, 0.51 mmol) added slowly via syringe. The reaction was warmed up to RT and stirred for 2 hrs. The reaction was cooled back to −5° C. and quenched with saturated aqueous solution of sodium thiosulfate. The product was extracted into EtOAc, and the organic layer was collected, dried over sodium sulfate and concentrated to afford a crude yellow residue. The residue was purified by ISCO silica gel chromatography (2-5% MeOH/DCM), and the purified fractions were further purified by Gilson RPLC in system (15%-85% CH3CN/H2O/0.1% TFA) to afford di-tert-butyl 3-(4-(2-(4-(4-phenylphthalazin-1-ylamino)phenoxy)pyridin-3-yl)pyrimidin-2-ylamino)propyl phosphate. MS m/z=734 [M+H]+. Calc'd for C40H44N7O5P: 733.8.

後処理

  1. temperaturecooled to −5° C.
  2. temperatureThe reaction was warmed up to RT
  3. stirringstirred for 2 hrs
  4. temperatureThe reaction was cooled back to −5° C.
  5. customquenched with saturated aqueous solution of sodium thiosulfate
  6. extractionThe product was extracted into EtOAc
  7. customthe organic layer was collected
  8. dry with materialdried over sodium sulfate
  9. concentrationconcentrated
  10. customto afford a crude yellow residue
  11. customThe residue was purified by ISCO silica gel chromatography (2-5% MeOH/DCM)
  12. customthe purified fractions were further purified by Gilson RPLC in system (15%-85% CH3CN/H2O/0.1% TFA)

出典と根拠

ORDレコード
ord-204647122c57404d87932925745e4493
出典データセット
uspto-grants-2009_07
特許番号
US07560551B2

反応ノート

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