Dimethyl Sulfoxide → HCID 21217719, compound

HRID 375882Notes

Reaction equation

HRID 375882 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. was added CH2Cl2 (5 ml) and DMSO (3.22 ml, 0.0454 mol). The reaction mixture was stirred for 1 hour then a solution of 1-ethyl-6-methoxy-N-(4-hydroxycyclohexyl methyl)-1H-pyrazolo-[3,4-b]quinolin-4-amine (1.8 g, 0.0051 mol) in CH2Cl2 (30 ml) was added and the reaction mixture was slowly warmed to 0° C. with stirring overnight. The reaction mixture was cooled to -78° C. and triethylamine (11 ml, 0.075 mol) was added. The reaction mixture was warmed to room temperature, stirred for 5 hours and then poured into water. The mixture was extracted with CH2Cl2 and the CH2Cl2 extracts were combined, washed with water, dried over MgSO4 and evaporated. The residue was purified by column chromatography on silica gel eluting with ethyl acetate to afford the product as the free base. The free base was dissolved in 2-propanol and methanesulfonic acid was added. The volume was reduced to about 5 ml, ether was added and the precipitated salt was 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 was cooled to -78° C.
  3. temperatureThe reaction mixture was warmed to room temperature
  4. stirringstirred for 5 hours
  5. extractionThe mixture was extracted with CH2Cl2
  6. washwashed with water
  7. dry with materialdried over MgSO4
  8. customevaporated
  9. customThe residue was purified by column chromatography on silica gel eluting with ethyl acetate
  10. customto afford the product as the free base
  11. additionwas added
  12. filtrationthe precipitated salt was collected by filtration
  13. customrecrystallized from 2-propanol/ether

Sources & evidence

ORD record
ord-baddb7b2707f4d0b9f75c54d6ab066d2
Source dataset
uspto-grants-1996_01
Patent number
US05488055

Reaction notes

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