Hydrogen Peroxide → HCID 68639349, compound

HRID 640022Notes

Reaction equation

HRID 640022 reaction equation
C([N:3](CC)[P:4]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])[O:5][C:6]([CH3:9])([CH3:8])[CH3:7])C.[F:17][C:18]1[C:23]([F:24])=[CH:22][CH:21]=[CH:20][C:19]=1[NH:25][C:26](=[O:57])[CH2:27][N:28]1[CH:32]=[C:31]([NH:33][C:34]2[C:43]3[C:38](=[CH:39][C:40]([O:46][CH2:47][CH2:48][CH2:49][N:50]([CH2:54][CH2:55][OH:56])[CH2:51][CH2:52][CH3:53])=[C:41]([O:44][CH3:45])[CH:42]=3)[N:37]=[CH:36][N:35]=2)[CH:30]=[N:29]1.N1C=NN=N1.OO.S(S([O-])=O)([O-])(=O)=[O:66].[Na+].[Na+].C(=O)(O)[O-].[Na+]>CN(C)C=O.O>[NH3:3].[P:4]([O:56][CH2:55][CH2:54][N:50]([CH2:49][CH2:48][CH2:47][O:46][C:40]1[CH:39]=[C:38]2[C:43]([C:34]([NH:33][C:31]3[CH:30]=[N:29][N:28]([CH2:27][C:26]([NH:25][C:19]4[CH:20]=[CH:21][CH:22]=[C:23]([F:24])[C:18]=4[F:17])=[O:57])[CH:32]=3)=[N:35][CH:36]=[N:37]2)=[CH:42][C:41]=1[O:44][CH3:45])[CH2:51][CH2:52][CH3:53])([O:5][C:6]([CH3:7])([CH3:8])[CH3:9])([O:10][C:11]([CH3:12])([CH3:13])[CH3:14])=[O:66]

Participants

10

Reactant 6

HCID 784Hydrogen Peroxide2×HCID 516892Sodium BicarbonateHCID 656671Sodium PyrosulfiteHCID 4251849Di-tert-butyl diethylphosphoramiditeHCID 67261418HCID 67261418, compoundHCID 178418441HCID 178418441, compound

Product 2

HCID 222AmmoniaHCID 68639349HCID 68639349, compoundYield 72.7%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

Di-tert-butyl diethylphosphoramidite (486 mg, 1.95 mmol) was added slowly to a solution of N-(2,3-difluorophenyl)-2-{4-[(7-{3-[(2-hydroxyethyl)(propyl)amino]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-1-yl}acetamide (740 mg, 1.3 mmol) and tetrazole (228 mg, 3.25 mmol) in dimethylformamide (7.4 ml) under argon. The mixture was stirred at ambient temperature for 45 minutes. Hydrogen peroxide (9 N, 288 μl, 2.6 mmol) was added at 0° C. and the reaction stirred for 1.5 hours at ambient temperature. An additional quantity of hydrogen peroxide (72 μl, 0.65 mmol) was added to the solution to complete the oxidation. The mixture was cooled to 0° C. and a saturated solution of sodium metabisulphite (388 mg, 2 ml) was added slowly with vigorous stirring. The mixture was stirred at ambient temperature for 20 minutes, diluted with water and the pH adjusted to 7 with an aqueous solution of sodium bicarbonate. The mixture was extracted with ethyl acetate (3×10 ml), dried and concentrated. Purification by silica gel chromatography, eluting with dichloromethane:methanol (98:2) followed by dichloromethane:methanolic ammonia (3 N) (9:1) yielded di-tert-butyl 2-[[3-({4-[(1-{2-[(2,3-difluorophenyl)amino]-2-oxoethyl}-1H-pyrazol-4-yl)amino]-6-methoxyquinazolin-7-yl}oxy)propyl](propyl)amino]ethyl phosphate (720 mg, 67% yield):

Workup

  1. stirringthe reaction stirred for 1.5 hours at ambient temperature
  2. temperatureThe mixture was cooled to 0° C.
  3. stirringThe mixture was stirred at ambient temperature for 20 minutes
  4. extractionThe mixture was extracted with ethyl acetate (3×10 ml)
  5. customdried
  6. concentrationconcentrated
  7. customPurification by silica gel chromatography
  8. washeluting with dichloromethane:methanol (98:2)

Sources & evidence

ORD record
ord-d9e691afe1914fc4a2d07aa5c53ec4ff
Source dataset
uspto-grants-2010_04
Patent number
US07691867B2

Reaction notes

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