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

HRID 227791Notes

Reaction equation

HRID 227791 reaction equation
[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]

Participants

7

Reactant 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, compound

Product 1

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

Procedure

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.

Workup

  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)

Sources & evidence

ORD record
ord-204647122c57404d87932925745e4493
Source dataset
uspto-grants-2009_07
Patent number
US07560551B2

Reaction notes

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