Water → 4-(7-(Bis((2-(trimethylsilyl)ethoxy)methyl)amino)pyrazolo[1,5-a]pyrimidin-5-yl)cyclohexanone

HRID 2368996Notes

Reaction equation

HRID 2368996 reaction equation
C=[C:2]1[CH2:7][CH2:6][CH:5]([C:8]2[CH:13]=[C:12]([N:14]([CH2:23][O:24][CH2:25][CH2:26][Si:27]([CH3:30])([CH3:29])[CH3:28])[CH2:15][O:16][CH2:17][CH2:18][Si:19]([CH3:22])([CH3:21])[CH3:20])[N:11]3[N:31]=[CH:32][CH:33]=[C:10]3[N:9]=2)[CH2:4][CH2:3]1.N1C(C)=CC=CC=1C.O.[O-:43]S([O-])(=S)=O.[Na+].[Na+]>O1CCOCC1.O=[Os](=O)(=O)=O>[CH3:30][Si:27]([CH3:29])([CH3:28])[CH2:26][CH2:25][O:24][CH2:23][N:14]([CH2:15][O:16][CH2:17][CH2:18][Si:19]([CH3:20])([CH3:21])[CH3:22])[C:12]1[N:11]2[N:31]=[CH:32][CH:33]=[C:10]2[N:9]=[C:8]([CH:5]2[CH2:4][CH2:3][C:2](=[O:43])[CH2:7][CH2:6]2)[CH:13]=1

Participants

7

Reactant 4

HCID 962WaterHCID 79372,6-LutidineHCID 24477Sodium ThiosulfateHCID 665839235-(4-methylenecyclohexyl)-N,N-bis((2-(trimethylsilyl)ethoxy)methyl)pyrazolo[1,5-a]pyrimidin-7-amine

Product 1

HCID 665836364-(7-(Bis((2-(trimethylsilyl)ethoxy)methyl)amino)pyrazolo[1,5-a]pyrimidin-5-yl)cyclohexanoneYield 73%

Reagents, catalysts & solvents 2

HCID 30318Osmium TetroxideCatalystHCID 312751,4-DioxaneSolvent

Procedure

To 5-(4-methylenecyclohexyl)-N,N-bis((2-(trimethylsilyl)ethoxy)methyl)pyrazolo[1,5-a]pyrimidin-7-amine (4.60 g, 9.41 mmol) in dioxane (50 mL) was added OsO4 (2.5 w % in tBuOH, 5 mol %), 2,6-Lutidine (4.37 mL, 37.6 mmol) and H2O (10 mL). The resulting mixture was stirred at room temperature for 20 min, then NaIO4 (8.05 g, 37.6 mmol) was added and the reaction mixture was stirred at room temperature overnight. LCMS showed very good conversion to the desired product (491). Na2S2O3 (sat.) was added and the mixture was stirred for 10 min. Dioxane was removed and the residue was extracted with EtOAc, washed with H2O and brine, dried over Na2SO4, and concentrated. The crude product was purified by a SiO2 column (0-40% EtOAc/Hexanes, Rf=0.15 in 20% EtOAc) to afford 4-(7-(bis((2-(trimethylsilyl)ethoxy)methyl)amino)pyrazolo[1,5-a]pyrimidin-5-yl)cyclohexanone as a colorless oil (3.37 g, 73%).

Workup

  1. stirringthe reaction mixture was stirred at room temperature overnight
  2. stirringthe mixture was stirred for 10 min
  3. customDioxane was removed
  4. extractionthe residue was extracted with EtOAc
  5. washwashed with H2O and brine
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated
  8. customThe crude product was purified by a SiO2 column (0-40% EtOAc/Hexanes, Rf=0.15 in 20% EtOAc)

Sources & evidence

ORD record
ord-c2e0662e8fda407a90de4ee1b455cf6c
Source dataset
uspto-grants-2014_04
Patent number
US08703784B2

Reaction notes

Loading…