3-Fluorobenzylamine → HCID 66936988, compound

HRID 1963861Notes

Reaction equation

HRID 1963861 reaction equation
[Cl:1][C:2]1[C:3]([C:22]2[CH:27]=[CH:26][CH:25]=[C:24](F)[N:23]=2)=[CH:4][C:5]([NH:8][CH:9]2[CH2:14][CH2:13][N:12]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:11][CH2:10]2)=[N:6][CH:7]=1.[F:29][C:30]1[CH:31]=[C:32]([CH2:36][NH2:37])[CH:33]=[CH:34][CH:35]=1>CS(C)=O>[Cl:1][C:2]1[C:3]([C:22]2[CH:27]=[CH:26][CH:25]=[C:24]([NH:37][CH2:36][C:32]3[CH:33]=[CH:34][CH:35]=[C:30]([F:29])[CH:31]=3)[N:23]=2)=[CH:4][C:5]([NH:8][CH:9]2[CH2:14][CH2:13][N:12]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:11][CH2:10]2)=[N:6][CH:7]=1

Participants

4

Reactant 2

HCID 668533-FluorobenzylamineHCID 66936941Tert-butyl 4-(5'-chloro-6-fluoro-2,4'-bipyridin-2'-yl-amino)piperidine-1-carboxylate

Product 1

HCID 66936988HCID 66936988, compoundYield 89.3%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of tert-butyl 4-(5′-chloro-6-fluoro-2,4′-bipyridin-2′-yl-amino)piperidine-1-carboxylate (200 mg, 0.492 mmol), DMSO (2 ml), TEA (0.137 ml, 0.983 mmol) and (3-fluorophenyl)methanamine (554 mg, 4.42 mmol) reaction mixture was flushed with argon and stirred at 100° C. for 40 hr, as the reaction mixture progress was followed by LCMS. The reaction mixture was cooled to room temperature, mixed with 150 ml of ethyl acetate, washed with saturated sodium bicarbonate (2×), water (3), saturated salt solution (1×), dried over sodium sulfate, filtered and concentrated to yield a crude material, which was purified by silica gel chromatography using a 12 g column, eluting from 0%-35% ethyl acetate with hexane. The desired fractions were collected and concentrated to constant mass, giving 225 mg of the title compound as a free base. LCMS (m/z): 512.3 (MH+), retention time=0.91 min.

Workup

  1. customwas flushed with argon
  2. temperatureThe reaction mixture was cooled to room temperature
  3. additionmixed with 150 ml of ethyl acetate
  4. washwashed with saturated sodium bicarbonate (2×), water (3), saturated salt solution (1×)
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customto yield a crude material, which
  9. customwas purified by silica gel chromatography
  10. washeluting from 0%-35% ethyl acetate with hexane
  11. customThe desired fractions were collected
  12. concentrationconcentrated to constant mass

Sources & evidence

ORD record
ord-6d40f058806348aab17aa1cd3b2bfdbd
Source dataset
uspto-grants-2013_04
Patent number
US08415381B2

Reaction notes

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