Dimethyl Sulfoxide → HCID 21217719, compound

HRID 1586166Notes

Reaction equation

HRID 1586166 reaction equation
FC(F)(F)C(OC(=O)C(F)(F)F)=O.CS(C)=O.[CH2:18]([N:20]1[C:24]2=[N:25][C:26]3[C:31]([C:32]([NH:33][CH2:34][CH:35]4[CH2:40][CH2:39][CH:38]([OH:41])[CH2:37][CH2:36]4)=[C:23]2[CH:22]=[N:21]1)=[CH:30][C:29]([O:42][CH3:43])=[CH:28][CH:27]=3)[CH3:19].C(N(CC)CC)C.CS(O)(=O)=O>C(Cl)Cl.CC(O)C.CCOCC.O>[CH2:18]([N:20]1[C:24]2=[N:25][C:26]3[C:31]([C:32]([NH:33][CH2:34][CH:35]4[CH2:40][CH2:39][C:38](=[O:41])[CH2:37][CH2:36]4)=[C:23]2[CH:22]=[N:21]1)=[CH:30][C:29]([O:42][CH3:43])=[CH:28][CH:27]=3)[CH3:19]

Participants

10

Reactant 5

HCID 679Dimethyl SulfoxideHCID 6395Methanesulfonic AcidHCID 8471TriethylamineHCID 9845Trifluoroacetic anhydrideHCID 98415311-ethyl-6-methoxy-N-(4-hydroxycyclohexylmethyl)-1H-pyrazolo[3,4-b]quinolin-4-amine

Product 1

HCID 21217719HCID 21217719, compoundYield 55.6%

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 3283Diethyl EtherSolventHCID 3776IsopropanolSolventHCID 6344DichloromethaneSolvent3×

Conditions

Temperature
0 °C

Procedure

To a solution of CH2Cl2 (35 ml) and trifluoroacetic anhydride (3.6 ml, 0.0224 mol) at -78° C. is added CH2Cl2 (5 ml) and DMSO (3.22 ml, 0.0454 mol). The reaction mixture is stirred for 1 hour, then a solution of 1-ethyl-6-methoxy-N-(4-hydroxycyclohexylmethyl)-1H-pyrazolo-[3,4-b]quinolin-4-amine (1.8 g, 0.0051 mol) in CH2Cl2 (30 ml) is added, and the reaction mixture is slowly warmed to 0° C. with stirring overnight. The reaction mixture is cooled to -78° C. and triethylamine (11 ml, 0.075 mol) is added. The reaction mixture is warmed to room temperature, stirred for 5 hours and then poured into water. The mixture is extracted with CH2Cl2 and the CH2Cl2 extracts are combined, washed with water, dried over MgSO4 and evaporated. The residue is purified by column chromatography on silica gel eluting with ethyl acetate to afford the product as the free base. The free base is dissolved in 2-propanol and methanesulfonic acid is added. The volume is reduced to about 5 ml, ether is added and the precipitated salt is collected by filtration and recrystallized from 2-propanol/ether to afford 1 g of 1-ethyl-6-methoxy-N-[4-oxocyclohexylmethyl]-1H-pyrazolo[3,4-b]quinolin-4-amine. CH3SO3H. 1/2 H2O.

Workup

  1. stirringwith stirring overnight
  2. temperatureThe reaction mixture is cooled to -78° C.
  3. temperatureThe reaction mixture is warmed to room temperature
  4. stirringstirred for 5 hours
  5. extractionThe mixture is extracted with CH2Cl2
  6. washwashed with water
  7. dry with materialdried over MgSO4
  8. customevaporated
  9. customThe residue is purified by column chromatography on silica gel eluting with ethyl acetate
  10. customto afford the product as the free base
  11. additionis added
  12. filtrationthe precipitated salt is collected by filtration
  13. customrecrystallized from 2-propanol/ether

Sources & evidence

ORD record
ord-6bf1d0165bdf4504867699d5d46599db
Source dataset
uspto-grants-1999_08
Patent number
US05942520

Reaction notes

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