Ether hydrochloride → Benzamide, 2,4,6-trifluoro-N-(6-((1-methyl-4-piperidinyl)carbonyl)-2-pyridinyl)-, hydrochloride (1:1)

HRID 1667350Notes

Reaction equation

HRID 1667350 reaction equation
[F:1][C:2]1[CH:25]=[C:24]([F:26])[CH:23]=[C:22]([F:27])[C:3]=1[C:4]([NH:6][C:7]1[CH:12]=[CH:11][CH:10]=[C:9]([C:13]([CH:15]2[CH2:20][CH2:19][N:18]([CH3:21])[CH2:17][CH2:16]2)=[O:14])[N:8]=1)=[O:5].C(OCC)C.[ClH:33]>C(O)(C)C>[ClH:33].[F:27][C:22]1[CH:23]=[C:24]([F:26])[CH:25]=[C:2]([F:1])[C:3]=1[C:4]([NH:6][C:7]1[CH:12]=[CH:11][CH:10]=[C:9]([C:13]([CH:15]2[CH2:20][CH2:19][N:18]([CH3:21])[CH2:17][CH2:16]2)=[O:14])[N:8]=1)=[O:5]

Participants

4

Reactant 2

HCID 10953452Ether hydrochlorideHCID 11610526Lasmiditan

Product 1

HCID 17980336Benzamide, 2,4,6-trifluoro-N-(6-((1-methyl-4-piperidinyl)carbonyl)-2-pyridinyl)-, hydrochloride (1:1)Yield 93%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Procedure

Dissolve 2,4,6-trifluoro-N-[6-(1-methylpiperidin-4-ylcarbonyl)-pyridin-2-yl]-benzamide-free base (5 g, 23.26 mmol) in isopropanol (50 mL) at room temperature and add a solution of 3.3 M diethylether/HCl (8 mL). Heat the reaction mixture under reflux for 30 minutes. Cool the reaction mixture to room temperature and agitate for 2 hrs. Filter the resulting white precipitate and rinse with isopropanol (5 mL). Dry the residual solid under reduce pressure at 40° C. overnight to obtain the title compound (5.12 g, 93% yield). M.p. 223-224° C. (sublimation); 1H NMR (400 MHz, d6-DMSO) d ppm 1.94 (m, 2H) 2.14 (m, J=11.15 Hz, 2H) 2.74 (s, 3H) 2.99 (m, J=9.19 Hz, 2H) 3.49 (m, J=11.15 Hz, 2H) 3.77 (m, 1H) 7.41 (t, J=8.71 Hz, 2H) 7.78 (d, J=7.43 Hz, 1H) 8.10 (t, J=7.92 Hz, 1H) 8.37 (d, J=6.85 Hz, 1H) 10.50 (s, 1H) 11.51 (s, 1H); 13C-NMR: (100.61 MHz, Chloroform-D) ppm 200.7; 130.6-158.0 (m, C-F-couplings); 150.4; 150.1; 140.2; 118.5; 118.2; 111.9; 101.3 (t, C-F couplings); 52.8; 42.6; 25.2

Workup

  1. temperatureHeat the reaction mixture
  2. temperatureunder reflux for 30 minutes
  3. filtrationFilter the resulting white precipitate
  4. washrinse with isopropanol (5 mL)
  5. customDry the residual solid
  6. customat 40° C.
  7. customovernight

Sources & evidence

ORD record
ord-46b787f3f1c648b7b6f99d8b09e003eb
Source dataset
uspto-grants-2011_10
Patent number
US08044207B2

Reaction notes

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