Potassium tert-butoxide → 1-(2-(tert-butyldimethylsilyloxy)-1-(4-chloro-3-fluorophenyl)ethyl)-4-(2-(methylthio)pyrimidin-4-yl)pyrimidin-2(1H)-one

HRID 1774186Notes

Reaction equation

HRID 1774186 reaction equation
CC([O-])(C)C.[K+].[CH3:7][S:8][C:9]1[N:14]=[C:13]([C:15]2[CH:20]=[CH:19][NH:18][C:17](=[O:21])[N:16]=2)[CH:12]=[CH:11][N:10]=1.CS(O[CH:27]([C:37]1[CH:42]=[CH:41][C:40]([Cl:43])=[C:39]([F:44])[CH:38]=1)[CH2:28][O:29][Si:30]([C:33]([CH3:36])([CH3:35])[CH3:34])([CH3:32])[CH3:31])(=O)=O>[I-].C([N+](CCCC)(CCCC)CCCC)CCC.C1COCC1>[Si:30]([O:29][CH2:28][CH:27]([N:18]1[CH:19]=[CH:20][C:15]([C:13]2[CH:12]=[CH:11][N:10]=[C:9]([S:8][CH3:7])[N:14]=2)=[N:16][C:17]1=[O:21])[C:37]1[CH:42]=[CH:41][C:40]([Cl:43])=[C:39]([F:44])[CH:38]=1)([C:33]([CH3:35])([CH3:36])[CH3:34])([CH3:32])[CH3:31]

Participants

6

Reactant 3

HCID 23665647Potassium tert-butoxideHCID 71726883HCID 71726883, compoundHCID 178503421HCID 178503421, compound

Product 1

HCID 866966841-(2-(tert-butyldimethylsilyloxy)-1-(4-chloro-3-fluorophenyl)ethyl)-4-(2-(methylthio)pyrimidin-4-yl)pyrimidin-2(1H)-oneYield 33%

Reagents, catalysts & solvents 2

HCID 67553Tetrabutylammonium IodideCatalystHCID 8028TetrahydrofuranSolvent2×

Procedure

Potassium 2-methylpropan-2-olate (0.026 g, 0.24 mmol) and tetrabutylammonium iodide (0.0067 g, 0.018 mmol) were added to 4-(2-(methylthio)pyrimidin-4-yl)pyrimidin-2(1H)-one (0.040 g, 0.18 mmol) suspended in THF (4 mL) cooled in ice. After 10 minutes, a solution of 2-(tert-butyldimethylsilyloxy)-1-(4-chloro-3-fluorophenyl)ethyl methanesulfonate (0.10 g, 0.27 mmol) in THF (1 mL) was added. The mixture was stirred at room temperature overnight and then heated at 90° C. for 3 days. Due to incomplete reaction, the material was transferred to a microwave vial and heated in a microwave at 130° C. for 1 hour. The reaction mixture was evaporated, and the residue was chromatographed on a 10 g Biotage SNAP column with 1:1 hexane/EtOAc. Fractions 8-13 contained the desired 1-(2-(tert-butyldimethylsilyloxy)-1-(4-chloro-3-fluorophenyl)ethyl)-4-(2-(methylthio)pyrimidin-4-yl)pyrimidin-2(1H)-one (0.030 g, 0.059 mmol, 33% yield) as a film.

Workup

  1. temperaturecooled in ice
  2. temperatureheated at 90° C. for 3 days
  3. customDue to incomplete reaction
  4. temperatureheated in a microwave at 130° C. for 1 hour
  5. customThe reaction mixture was evaporated
  6. customthe residue was chromatographed on a 10 g Biotage SNAP column with 1:1 hexane/EtOAc

Sources & evidence

ORD record
ord-f70beae1ac0f46688a2b14e378fea5de
Source dataset
uspto-grants-2016_02
Patent number
US09259470B2

Reaction notes

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