4-Fluoroaniline → HCID 118037407, compound

HRID 1509039Notes

Reaction equation

HRID 1509039 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([C:8]2[CH:13]=[CH:12][CH:11]=[C:10]([Cl:14])[CH:9]=2)[N:5]=[C:4]2[CH2:15][CH2:16][CH2:17][C:3]=12.[F:18][C:19]1[CH:25]=[CH:24][C:22]([NH2:23])=[CH:21][CH:20]=1.C(=O)(O)[O-].[Na+]>Cl.CN1C(=O)CCC1.O>[ClH:1].[Cl:14][C:10]1[CH:9]=[C:8]([C:6]2[N:5]=[C:4]3[CH2:15][CH2:16][CH2:17][C:3]3=[C:2]([NH:23][C:22]3[CH:24]=[CH:25][C:19]([F:18])=[CH:20][CH:21]=3)[CH:7]=2)[CH:13]=[CH:12][CH:11]=1

Participants

7

Reactant 3

HCID 97314-FluoroanilineHCID 516892Sodium BicarbonateHCID 901106754-chloro-2-(3-chlorophenyl)-6,7-dihydro-5H-cyclopenta[b]pyridine

Product 1

HCID 118037407HCID 118037407, compoundYield 70%

Reagents, catalysts & solvents 3

HCID 313Hydrochloric AcidCatalystHCID 962WaterSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
120 °C

Procedure

A 10-mL microwave vial was charged with 4-chloro-2-(3-chlorophenyl)-6,7-dihydro-5H-cyclopenta[b]pyridine (0.072 g, 0.27 mmol), 4-fluoroaniline (0.052 mL, 0.54 mmol) and cone. HCl (1 drop) in NMP (2 mL). The resulting mixture was heated at 120° C. under microwave irradiation for 3 h. After this time, the reaction mixture was cooled, diluted with water (25 mL) then treated with saturated sodium bicarbonate until pH˜8 and extracted with ethyl acetate. The combined extract was washed with saturated sodium chloride, dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by chromatography on silica using hexanes/ethyl acetate (10:0 to 1:1) as the eluent to afford the free base of the title compound (0.064 g, 70%) as an oil. MW=338.81. 1H NMR (DMSO-d6, 500 MHz) δ 8.14 (s, 1H), 7.93-7.90 (m, 1H), 7.76 (dt, J=7.0, 2.0 Hz, 1H), 7.45-7.39 (m, 2H), 7.31-7.26 (m, 2H), 7.24-7.18 (m, 2H), 7.13 (s, 1H), 2.91 (t, J=7.5 Hz, 2H), 2.82 (t, J=7.5 Hz, 2H), 2.09 (quin, J=7.5 Hz, 2H). Treatment with 1.25M HCl in methanol (0.15 mL, 0.19 mmol, 1.0 eq.) afforded the title compound (0.064 g, 91%) as a white solid. MW=375.27. M.p. 103-106° C. 1H NMR (DMSO-d6, 500 MHz) δ 13.99 (br s, 1H), 9.05 (br s, 1H), 7.92-7.89 (m, 1H), 7.75-7.70 (m, 1H), 7.57-7.49 (m, 2H), (m, 2H), 7.31-7.25 (m, 2H), 7.04 (s, 1H), 3.04 (t, J=7.5 Hz, 2H), 2.87 (t, J=7.5 Hz, 2H), 2.17 (quin, J=7.5 Hz, 2H); ESI MS m/z 339 [m+H]+.

Workup

  1. temperatureAfter this time, the reaction mixture was cooled
  2. extractionextracted with ethyl acetate
  3. extractionThe combined extract
  4. washwas washed with saturated sodium chloride
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified by chromatography on silica

Sources & evidence

ORD record
ord-8103eb73d1604a8f9db104143cd6f412
Source dataset
uspto-grants-2015_12
Patent number
US09221843B2

Reaction notes

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