p-Toluenesulfonic acid → HCID 86722463, compound

HRID 718849Notes

Reaction equation

HRID 718849 reaction equation
[NH2:1][C:2]1[N:6]([C:7]2[CH:12]=[CH:11][C:10]([F:13])=[CH:9][CH:8]=2)[N:5]=[CH:4][C:3]=1[CH:14]=O.[C:16]1(=O)[CH2:21][CH2:20][CH2:19][C:18](=[O:22])[CH2:17]1.CC1C=CC(S(O)(=O)=O)=CC=1>C1(C)C=CC=CC=1>[F:13][C:10]1[CH:9]=[CH:8][C:7]([N:6]2[C:2]3=[N:1][C:16]4[CH2:21][CH2:20][CH2:19][C:18](=[O:22])[C:17]=4[CH:14]=[C:3]3[CH:4]=[N:5]2)=[CH:12][CH:11]=1

Participants

5

Reactant 3

HCID 6101p-Toluenesulfonic acidHCID 104341,3-CyclohexanedioneHCID 86722462HCID 86722462, compound

Product 1

HCID 86722463HCID 86722463, compoundYield 70%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

A flask was charged with 5-amino-1-(4-fluorophenyl)-1H-pyrazole-4-carbaldehyde (111, R1=4-Fluorophenyl) (58.15 g, 283 mmol, cyclohexane-1,3-dione (47.7 g, 425 mmol) and toluene (600 mL). The slurry was stirred then pTSA (4.8 g, 25.2 mmol) was added. The mixture was warmed in an oil bath heated to about 100° C. for about 1 h. The mixture was allowed to cool to rt and stir overnight. The mixture was concentrated to dryness under reduced pressure. Water (400 mL), sat. aq. NaHCO3 (50 mL) and ethanol (100 mL) were added to the mixture. The supernatant was decanted and the solids were triturated with water (100 mL). The supernatant was decanted and the process repeated with another portion of water (100 mL). The solids were dried under reduced pressure to remove residual water. The material was stirred with MeOH (160 mL) then the solids were collected by filtration and washed with MeOH (80 mL). The material was dried under vacuum at about 65° C. to yield 1-(4-fluorophenyl)-7,8-dihydro-1H-pyrazolo[3,4-b]quinolin-5(6H)-one (112, R1=4-Fluorophenyl) (55.5 g, 70%); LC/MS, method 3, Rt=2.37 min, MS m/z 282 (M+H)+. 1H NMR (400 MHz, DMSO) δ 8.82 (s, 1H), 8.56 (s, 1H), 8.32-8.23 (m, 2H), 7.51-7.39 (m, 2H), 3.22 (t, J=6.2 Hz, 2H), 2.76-2.69 (t, J=6.0 Hz, 2H), 2.20-2.11 (m, 2H).

Workup

  1. temperatureThe mixture was warmed in an oil bath
  2. temperatureto cool to rt
  3. stirringstir overnight
  4. concentrationThe mixture was concentrated to dryness under reduced pressure
  5. additionWater (400 mL), sat. aq. NaHCO3 (50 mL) and ethanol (100 mL) were added to the mixture
  6. customThe supernatant was decanted
  7. customthe solids were triturated with water (100 mL)
  8. customThe supernatant was decanted
  9. customThe solids were dried under reduced pressure
  10. customto remove residual water
  11. stirringThe material was stirred with MeOH (160 mL)
  12. filtrationthe solids were collected by filtration
  13. washwashed with MeOH (80 mL)
  14. customThe material was dried under vacuum at about 65° C.

Sources & evidence

ORD record
ord-1d1598b76759467b8aa3417ba68390c6
Source dataset
uspto-grants-2015_11
Patent number
US09193744B2

Reaction notes

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