Dimethyl Sulfoxide → 1-ethyl-6-methoxy-N-(4-hydroxycyclohexylmethyl)-1H-pyrazolo[3,4-b]quinolin-4-amine

HRID 1586156Notes

Reaction equation

HRID 1586156 reaction equation
[OH:1][CH:2]1[CH2:7][CH2:6][CH:5]([CH2:8][NH2:9])[CH2:4][CH2:3]1.[CH2:10]([N:12]1[C:16]2=[N:17][C:18]3[C:23]([C:24](Cl)=[C:15]2[CH:14]=[N:13]1)=[CH:22][C:21]([O:26][CH3:27])=[CH:20][CH:19]=3)[CH3:11].CS(C)=O.CCOCC>CO>[CH2:10]([N:12]1[C:16]2=[N:17][C:18]3[C:23]([C:24]([NH:9][CH2:8][CH:5]4[CH2:6][CH2:7][CH:2]([OH:1])[CH2:3][CH2:4]4)=[C:15]2[CH:14]=[N:13]1)=[CH:22][C:21]([O:26][CH3:27])=[CH:20][CH:19]=3)[CH3:11]

Participants

6

Reactant 4

HCID 679Dimethyl SulfoxideHCID 3283Diethyl EtherHCID 148675294-(Aminomethyl)cyclohexan-1-olHCID 195922121-ethyl-4-chloro-6-methoxy-1H-pyrazolo[3,4-b]quinoline

Product 1

HCID 98415311-ethyl-6-methoxy-N-(4-hydroxycyclohexylmethyl)-1H-pyrazolo[3,4-b]quinolin-4-amineYield 31.3%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A mixture of 4-hydroxycyclohexylmethylamine (2.2 g, 17.05 mmol), 1-ethyl-4-chloro-6-methoxy-1H-pyrazolo[3,4-b]quinoline (2.0 g, 7.66 mmol) and DMSO is heated at 110°-120° C. under a nitrogen atmosphere for 16 hours. The reaction mixture is poured into ice water, and the mixture is extracted with CH2Cl2 (4×50 ml). The organic layers are combined, dried over MgSO4 and evaporated to dryness. The residue is purified by column chromatography on silica gel eluting with CH2Cl2 /methanol (9/1), followed by a second silica gel column eluting with ethyl acetate to afford 1.3 g of crude product. The crude product is dissolved in warm methanol, cooled to room temperature and treated with an equivalent amount of methanesuflonic acid. Ether is added to the mixture and the solid which forms is collected by filtration, washed with ether and recrystallized from isopropanol to afford 0.85 g of 1-ethyl-6-methoxy-N-(4-hydroxycyclohexylmethyl)-1H-pyrazolo[3,4-b]quinolin-4-amine. CH3SO3H, as yellow crystals, m.p. 256°-258° C. (dec.)

Workup

  1. temperatureis heated at 110°-120° C. under a nitrogen atmosphere for 16 hours
  2. extractionthe mixture is extracted with CH2Cl2 (4×50 ml)
  3. dry with materialdried over MgSO4
  4. customevaporated to dryness
  5. customThe residue is purified by column chromatography on silica gel eluting with CH2Cl2 /methanol (9/1)
  6. washeluting with ethyl acetate
  7. customto afford 1.3 g of crude product
  8. additiontreated with an equivalent amount of methanesuflonic acid
  9. filtrationthe solid which forms is collected by filtration
  10. washwashed with ether
  11. customrecrystallized from isopropanol

Sources & evidence

ORD record
ord-85b344d89905413e9c2070b55b00d2ec
Source dataset
uspto-grants-1999_08
Patent number
US05942520

Reaction notes

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