Potassium bis(trimethylsilyl)amide → HCID 86696705, compound

HRID 1774204Notes

Reaction equation

HRID 1774204 reaction equation
C[Si]([N-][Si](C)(C)C)(C)C.[K+].[O:11]1[CH2:16][CH2:15][CH:14]([NH:17][C:18]2[N:23]=[C:22]([C:24]3[CH:29]=[CH:28][NH:27][C:26](=[O:30])[CH:25]=3)[CH:21]=[CH:20][N:19]=2)[CH2:13][CH2:12]1.CS(O[C@H:36]([C:47]1[CH:52]=[CH:51][C:50]([Cl:53])=[C:49]([F:54])[CH:48]=1)[CH2:37][CH2:38][O:39][Si:40]([C:43]([CH3:46])([CH3:45])[CH3:44])([CH3:42])[CH3:41])(=O)=O>CC1CCCO1>[Si:40]([O:39][CH2:38][CH2:37][C@@H:36]([N:27]1[CH:28]=[CH:29][C:24]([C:22]2[CH:21]=[CH:20][N:19]=[C:18]([NH:17][CH:14]3[CH2:15][CH2:16][O:11][CH2:12][CH2:13]3)[N:23]=2)=[CH:25][C:26]1=[O:30])[C:47]1[CH:52]=[CH:51][C:50]([Cl:53])=[C:49]([F:54])[CH:48]=1)([C:43]([CH3:46])([CH3:45])[CH3:44])([CH3:42])[CH3:41]

Participants

5

Reactant 3

HCID 3251421Potassium bis(trimethylsilyl)amideHCID 71726884HCID 71726884, compoundHCID 86696649HCID 86696649, compound

Product 1

HCID 86696705HCID 86696705, compoundYield 66.5%

Reagents, catalysts & solvents 1

HCID 73012-MethyltetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

Potassium bis(trimethylsilyl)amide (0.91M in THF, 0.202 mL) was added to a cooled to 0° C. suspension of 4-(2-((tetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)pyridin-2(1H)-one (40 mg, 0.147 mmol) in 2-methyltetrahydrofuran (4 mL) The mixture was agitated 15 minutes, and (S)-3-(tert-butyldimethylsilyloxy)-1-(4-chloro-3-fluorophenyl)propyl methanesulfonate (81.6 mg, 0.206 mmol) in 2-methyltetrahydrofuran (1 mL) was added. The mixture was then heated to 75° C. and agitated overnight. The reaction was quenched with saturated sodium bicarbonate solution and diluted with ethyl acetate (5 mL). The organic layer was washed with water (2×) and evaporated. Purified by chromatography on silica gel, eluted with 50-75% ethyl acetate/hexanes to give (R)-1-(3-(tert-butyldimethylsilyloxy)-1-(4-chloro-3-fluorophenyl)propyl)-4-(2-((tetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)pyridin-2(1H)-one (0.056 g, 0.0977 mmol, 66.5% yield) as thick oil.

Workup

  1. temperatureThe mixture was then heated to 75° C.
  2. stirringagitated overnight
  3. customThe reaction was quenched with saturated sodium bicarbonate solution
  4. additiondiluted with ethyl acetate (5 mL)
  5. washThe organic layer was washed with water (2×)
  6. customevaporated
  7. customPurified by chromatography on silica gel
  8. washeluted with 50-75% ethyl acetate/hexanes

Sources & evidence

ORD record
ord-b71aecae812f4a6aa6b3a1864b175255
Source dataset
uspto-grants-2016_02
Patent number
US09259470B2

Reaction notes

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