Hydrogen Peroxide → HCID 86686136, compound

HRID 869183Notes

Reaction equation

HRID 869183 reaction equation
[C:1]([CH2:3][C:4]1[S:8][C:7]([C:9]2[N:14]=[N:13][C:12]([N:15]([CH2:23][C:24]3([C:28]4[C:33]([F:34])=[CH:32][CH:31]=[CH:30][N:29]=4)[CH2:27][CH2:26][CH2:25]3)[C:16](=[O:22])[O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[CH:11][CH:10]=2)=[N:6][CH:5]=1)#[N:2].C(=O)([O-])[O-:36].[K+].[K+].OO>CS(C)=O.CCOC(C)=O.O>[NH2:2][C:1](=[O:36])[CH2:3][C:4]1[S:8][C:7]([C:9]2[N:14]=[N:13][C:12]([N:15]([CH2:23][C:24]3([C:28]4[C:33]([F:34])=[CH:32][CH:31]=[CH:30][N:29]=4)[CH2:25][CH2:26][CH2:27]3)[C:16](=[O:22])[O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[CH:11][CH:10]=2)=[N:6][CH:5]=1

Participants

7

Reactant 3

HCID 784Hydrogen PeroxideHCID 11430Potassium CarbonateHCID 68231864HCID 68231864, compound

Product 1

HCID 86686136HCID 86686136, compoundYield 47.8%

Reagents, catalysts & solvents 3

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of t-butyl 6-(5-(cyanomethyl)thiazol-2-yl)pyridazin-3-yl((1-(3-fluoropyridin-2-yl)cyclobutyl)methyl)carbamate (12.5 g, 26.0 mmol) in DMSO (260 mL) was added potassium carbonate (14.4 g, 104.1 mmol). The mixture was cooled to 0° C. and hydrogen peroxide (86 mL) was slowly added. The reaction was warmed to rt and stirred for 90 min. The reaction was diluted with EtOAc (200 mL) and water (500 mL), and the organic layer was washed three times with brine (150 mL). The organic layer was then dried over Na2SO4, filtered, and concentrated to give a crude solid that was purified by silica gel chromatography (CH3CN/CH2Cl2) to afford 6.2 g of t-butyl 6-(5-(2-amino-2-oxoethyl)thiazol-2-yl)pyridazin-3-yl((1-(3-fluoropyridin-2-yl)cyclobutyl)methyl)carbamate as a reddish solid. This compound was combined with other batches (15.5 g overall), dissolved in 25% TFA/CH2Cl2, and stirred for 1 h. The reaction was then concentrated, dissolved in ethyl acetate (75 mL), and washed three times with potassium carbonate. The organic layer was then dried over Na2SO4, filtered, and concentrated to give a crude solid that was recrystallized with THF to give 10.8 g of 1-(2-((-3-fluoro-1-(3-fluoropyridin-2-yl)cyclobutyl)methylamino)pyrimidin-5-yl)-1H-pyrrole-3-carboxamide as an off-white solid (M+H=399.1).

Workup

  1. temperatureThe reaction was warmed to rt
  2. washthe organic layer was washed three times with brine (150 mL)
  3. dry with materialThe organic layer was then dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customto give a crude solid that
  7. customwas purified by silica gel chromatography (CH3CN/CH2Cl2)

Sources & evidence

ORD record
ord-3b3b3d06823549d39ddb589651f90753
Source dataset
uspto-grants-2015_03
Patent number
US08969346B2

Reaction notes

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