Potassium Carbonate → HCID 68153986, compound

HRID 341099Notes

Reaction equation

HRID 341099 reaction equation
F[C:2]1[C:11]2[N:10]([CH2:12][C:13]3[CH:18]=[CH:17][C:16]([N:19]4[CH:23]=[CH:22][CH:21]=[N:20]4)=[CH:15][CH:14]=3)[CH:9]=[C:8]3[C:24](=[O:34])[N:25]([C:27]4[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=4[F:33])[N:26]=[C:7]3[C:6]=2[C:5](F)=[CH:4][CH:3]=1.Cl.Cl.[F:38][C:39]1[C:40]([NH:45][C@@H:46]2[CH2:51][CH2:50][CH2:49][CH2:48][C@H:47]2[NH2:52])=[N:41][CH:42]=[CH:43][CH:44]=1.C(=O)([O-])[O-].[K+].[K+]>CS(C)=O>[F:33][C:28]1[CH:29]=[CH:30][CH:31]=[CH:32][C:27]=1[N:25]1[C:24](=[O:34])[C:8]2=[CH:9][N:52]([C@@H:47]3[CH2:48][CH2:49][CH2:50][CH2:51][C@H:46]3[NH:45][C:40]3[C:39]([F:38])=[CH:44][CH:43]=[CH:42][N:41]=3)[C:5]3[CH:4]=[CH:3][CH:2]=[C:11]([NH:10][CH2:12][C:13]4[CH:18]=[CH:17][C:16]([N:19]5[CH:23]=[CH:22][CH:21]=[N:20]5)=[CH:15][CH:14]=4)[C:6]=3[C:7]2=[N:26]1

Participants

5

Reactant 3

HCID 11430Potassium Carbonate2×HCID 68153837HCID 68153837, compoundHCID 68154060HCID 68154060, compound2×

Product 1

HCID 68153986HCID 68153986, compound

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
95 °C

Procedure

6,9-Difluoro-2-(2-fluorophenyl)-5-{[4-(1H pyrazol-1-yl)phenyl]methyl}-2,5-dihydro-3H-pyrazolo[4,3-c]quinolin-3-one (Example 28, 74 mg, 0.16 mmol), (±)-trans-N-(3-fluoropyridin-2-yl)cyclohexane-1,2-diamine bishydrochloride (43 mg, 0.19 mmol, 1.2 equiv) and potassium carbonate (0.22 g, 1.6 mmol, 10 equiv) were combined in degassed dimethylsulfoxide (5 mL) and placed into an oil bath preheated at 95° C. for 1 hour. Additional (±)-trans-N-(3-fluoropyridin-2-yl)cyclohexane-1,2-diamine bishydrochloride (0.10 g, 0.44 mmol, 2.3 equiv) and potassium carbonate (0.42 g, 3.0 mmol, 16 equiv) were added and the mixture was heated at 95° C. for an additional 2 hours. The mixture was cooled to ambient temperature, filtered and purified by preparative reverse phase HPLC (eluting 70:30 to 5:95; water containing 0.1% TFA: acetonitrile containing 0.1% TFA). The appropriate fractions were poured into sodium bicarbonate (100 mL, aqueous saturated) and extracted with ethyl acetate (1×50 mL). The organic extract was dried with sodium sulfate, filtered and concentrated in vacuo, providing the titled compound as a light yellowish-green solid: 1H-NMR (400 MHz, CDCl3) δ 8.73 (1H, s), 8.32 (1H, br s), 7.85 (1H, d, J=2.8 Hz), 7.77 (1H, d, J=4.6 Hz), 7.69 (1H, d, J=1.8 Hz), 7.61-7.56 (3H, m), 7.44 (2H, d, J=8.6 Hz), 7.30-7.24 (1H, m), 7.21-7.15 (2H, m), 7.11 (1H, dd, J=13.6, 9.8 Hz), 6.90 (1H, ddd, J=11.2, 7.9, 1.3 Hz), 6.83 (1H, dd, J=9.4, 3.0 Hz), 6.44 (1H, dd, J=2.4, 1.9 Hz), 6.39 (1H, ddd, J=7.9, 5.0, 3.5 Hz), 4.77-4.67 (3H, m), 4.56 (1H, br t, J=10.2 Hz), 4.35 (1H, br m), 2.33 (1H, br d, J=10.9 Hz), 2.23 (1H, br d, J=12.8 Hz), 2.01-1.79 (3H, m), 1.67-1.51 (3H, m) ppm; high resolution mass spectrometry (ES+) m/z 661.2621 [(M+H)+; calculated for C37H32F3N8O: 661.2646].

Workup

  1. customplaced into an oil bath
  2. temperatureThe mixture was cooled to ambient temperature
  3. filtrationfiltered
  4. custompurified by preparative reverse phase HPLC (eluting 70:30 to 5:95; water containing 0.1% TFA: acetonitrile containing 0.1% TFA)
  5. additionThe appropriate fractions were poured into sodium bicarbonate (100 mL, aqueous saturated)
  6. extractionextracted with ethyl acetate (1×50 mL)
  7. extractionThe organic extract
  8. dry with materialwas dried with sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-5bc65739215942f3a7a487c52b53193c
Source dataset
uspto-grants-2014_11
Patent number
US08895580B2

Reaction notes

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