Ethyl 1-(benzyloxymethyl)-4-(7-(bis((2-(trimethylsilyl)ethoxy)methyl)amino)pyrazolo[1,5-a]pyrimidin-5-yl)cyclohex-3-enecarboxylate → Ethyl 4-(7-(bis((2-(trimethylsilyl)ethoxy)methyl)amino)pyrazolo[1,5-a]pyrimidin-5-yl)-1-(hydroxymethyl)cyclohexanecarboxylate

HRID 334365Notes

Reaction equation

HRID 334365 reaction equation
C([O:8][CH2:9][C:10]1([C:42]([O:44][CH2:45][CH3:46])=[O:43])[CH2:15][CH2:14][C:13]([C:16]2[CH:21]=[C:20]([N:22]([CH2:31][O:32][CH2:33][CH2:34][Si:35]([CH3:38])([CH3:37])[CH3:36])[CH2:23][O:24][CH2:25][CH2:26][Si:27]([CH3:30])([CH3:29])[CH3:28])[N:19]3[N:39]=[CH:40][CH:41]=[C:18]3[N:17]=2)=[CH:12][CH2:11]1)C1C=CC=CC=1>C1COCC1.[Pd]>[CH3:29][Si:27]([CH3:28])([CH3:30])[CH2:26][CH2:25][O:24][CH2:23][N:22]([CH2:31][O:32][CH2:33][CH2:34][Si:35]([CH3:38])([CH3:37])[CH3:36])[C:20]1[N:19]2[N:39]=[CH:40][CH:41]=[C:18]2[N:17]=[C:16]([CH:13]2[CH2:12][CH2:11][C:10]([CH2:9][OH:8])([C:42]([O:44][CH2:45][CH3:46])=[O:43])[CH2:15][CH2:14]2)[CH:21]=1

Participants

4

Reactant 1

HCID 86686664Ethyl 1-(benzyloxymethyl)-4-(7-(bis((2-(trimethylsilyl)ethoxy)methyl)amino)pyrazolo[1,5-a]pyrimidin-5-yl)cyclohex-3-enecarboxylate

Product 1

HCID 66584374Ethyl 4-(7-(bis((2-(trimethylsilyl)ethoxy)methyl)amino)pyrazolo[1,5-a]pyrimidin-5-yl)-1-(hydroxymethyl)cyclohexanecarboxylateYield 27.6%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
50 °C

Procedure

A mixture of ethyl 1-(benzyloxymethyl)-4-(7-(bis((2-(trimethylsilyl)ethoxy)methyl)amino)pyrazolo[1,5-a]pyrimidin-5-yl)cyclohex-3-enecarboxylate (3.06 g, 4.59 mmol) and Pd/C (cat.) in THF (25 mL) was heated at 50° C. under 1.0 atm of H2 for 16 h. LCMS indicated complete reduction of double bond. The reaction mixture was filtered and evaporated. The residue was dissolved in MeOH and HCO2NH4 and Pd/C (cat.) was added. The resulting mixture was heated under reflux for 24 h. After cooling to rt, the reaction mixture was filtered. The filtrate was concentrated and purified by a SiO2 column (0-40% EtOAc/Hexanes, Rf=0.5 in 50% EtOAc) to afford ethyl 4-(7-(bis((2-(trimethylsilyl)ethoxy)methyl)amino)pyrazolo[1,5-a]pyrimidin-5-yl)-1-(hydroxymethyl)cyclohexanecarboxylate as colorless oil (733 mg). HPLC-MS TR=2.78 min (UV 254 nm, 5 min method); mass calculated for formula C28H50N4O5Si2 578.3, observed LCMS m/z 579.2 (M+H).

Workup

  1. filtrationThe reaction mixture was filtered
  2. customevaporated
  3. dissolutionThe residue was dissolved in MeOH
  4. additionHCO2NH4 and Pd/C (cat.) was added
  5. temperatureThe resulting mixture was heated
  6. temperatureunder reflux for 24 h
  7. temperatureAfter cooling to rt
  8. filtrationthe reaction mixture was filtered
  9. concentrationThe filtrate was concentrated
  10. custompurified by a SiO2 column (0-40% EtOAc/Hexanes, Rf=0.5 in 50% EtOAc)

Sources & evidence

ORD record
ord-96d0414c7d2548a6be071e5ad75eb1e7
Source dataset
uspto-grants-2014_11
Patent number
US08883801B2

Reaction notes

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