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

HRID 334356Notes

Reaction equation

HRID 334356 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)cyclohexanone

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 rt for 20 min, then NaIO4 (8.05 g, 37.6 mmol) was added and the reaction mixture was stirred at rt 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). HPLC-MS TR=2.84 min (UV 254 nm, 5 min method); mass calculated for formula C24H42N4O3Si2 490.3, observed LCMS m/z 491.2 (M+H).

Workup

  1. stirringthe reaction mixture was stirred at rt 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-9d0d671cca004044acd3b74444644f9d
Source dataset
uspto-grants-2014_11
Patent number
US08883801B2

Reaction notes

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