Hydrogen Peroxide → 8-[5-(3-Methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]-1,4-dioxaspiro[4.5]decane-8-carboxamide

HRID 1040004Notes

Reaction equation

HRID 1040004 reaction equation
[CH3:1][C:2]1[CH:3]=[C:4]([C:19]2[S:23][C:22]([C:24]3([C:34]#[N:35])[CH2:33][CH2:32][C:27]4([O:31][CH2:30][CH2:29][O:28]4)[CH2:26][CH2:25]3)=[N:21][CH:20]=2)[CH:5]=[C:6]([NH:8][C:9]2[N:14]=[C:13]([C:15]([F:18])([F:17])[F:16])[CH:12]=[CH:11][N:10]=2)[CH:7]=1.C(=O)([O-])[O-:37].[K+].[K+].OO>CS(C)=O.O>[CH3:1][C:2]1[CH:3]=[C:4]([C:19]2[S:23][C:22]([C:24]3([C:34]([NH2:35])=[O:37])[CH2:25][CH2:26][C:27]4([O:28][CH2:29][CH2:30][O:31]4)[CH2:32][CH2:33]3)=[N:21][CH:20]=2)[CH:5]=[C:6]([NH:8][C:9]2[N:14]=[C:13]([C:15]([F:17])([F:18])[F:16])[CH:12]=[CH:11][N:10]=2)[CH:7]=1

Participants

6

Reactant 3

HCID 784Hydrogen PeroxideHCID 11430Potassium CarbonateHCID 672617008-[5-(3-Methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]-1,4-dioxaspiro[4.5]decane-8-carbonitrile

Product 1

HCID 672577948-[5-(3-Methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]-1,4-dioxaspiro[4.5]decane-8-carboxamideYield 63%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolvent

Conditions

Temperature
70 °C

Procedure

To a solution of 8-[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]-1,4-dioxaspiro[4.5]decane-8-carbonitrile (250 mg, 0.50 mmol) in anhydrous DMSO (4 ml) were added potassium carbonate (172 mg, 1.25 mmol) and hydrogen peroxide (218 μL, 2.49 mmol). The resulting solution was stirred at 70° C. for 1.5 h, cooled to room temperature and diluted with water (70 ml) and washed with EtOAc (2×60 ml). The combined organic layers were dried over Na2SO4, filtered and concentrated. The crude oil was triturated with diethyl ether and hexanes, and the resulting tan solid was collected via filtration and air dried to provide 8-[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]-1,4-dioxaspiro[4.5]decane-8-carboxamide (171 mg, 0.31 mmol, 63% yield) as a tan solid. MS ESI: [M+H]+ m/z 520.1. 1H NMR (500 MHz, CD3OD): δ 11.0 (s, 1H), 9.64 (d, 1H, J=4.9 Hz), 8.79 (s, 1H), 8.76 (bs, 1H), 8.28 (bs, 1H), 8.12-8.05 (m, 3H), 7.97 (s, 1H), 4.68-4.64 (m, 4H), 3.23-3.15 (m, 2H), 3.12 (s, 3H), 2.95-2.85 (m, 2H), 2.44-2.38 (m, 4H).

Workup

  1. temperaturecooled to room temperature
  2. washwashed with EtOAc (2×60 ml)
  3. dry with materialThe combined organic layers were dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude oil was triturated with diethyl ether and hexanes
  7. filtrationthe resulting tan solid was collected via filtration and air
  8. customdried

Sources & evidence

ORD record
ord-460902c8a62340fcb8bbde2359c9ed75
Source dataset
uspto-grants-2013_10
Patent number
US08551984B2

Reaction notes

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