Hydrochloric Acid → HCID 66876268, compound

HRID 1666337Notes

Reaction equation

HRID 1666337 reaction equation
[ClH:1].[NH:2]1[CH2:7][CH2:6][C:5](=[CH:8][C:9]2[CH:10]=[C:11]([CH:23]=[CH:24][CH:25]=2)[O:12][C:13]2[CH:18]=[CH:17][C:16]([C:19]([F:22])([F:21])[F:20])=[CH:15][N:14]=2)[CH2:4][CH2:3]1.[C:26]([C:28]1[N:33]=[CH:32][C:31]([NH:34][C:35](=O)[O:36]C2C=CC=CC=2)=[CH:30][CH:29]=1)#[N:27].NC1C=NC(C#N)=CC=1.C(N(C(C)C)CC)(C)C.Cl>CS(C)=O.C(OCC)C>[ClH:1].[C:26]([C:28]1[N:33]=[CH:32][C:31]([NH:34][C:35]([N:2]2[CH2:7][CH2:6][C:5](=[CH:8][C:9]3[CH:25]=[CH:24][CH:23]=[C:11]([O:12][C:13]4[CH:18]=[CH:17][C:16]([C:19]([F:22])([F:20])[F:21])=[CH:15][N:14]=4)[CH:10]=3)[CH2:4][CH2:3]2)=[O:36])=[CH:30][CH:29]=1)#[N:27]

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 81531DiisopropylethylamineHCID 38713955-Aminopyridine-2-carbonitrileHCID 59275888HCID 59275888, compoundHCID 668761612-(3-(Piperidin-4-ylidenemethyl)phenoxy)-5-(trifluoromethyl)pyridine hydrochloride

Product 1

HCID 66876268HCID 66876268, compoundYield 56%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 3283Diethyl EtherSolvent2×

Conditions

Temperature
50 °C

Procedure

A solution of 2-(3-piperidin-4-ylidenemethyl-phenoxy)-5-trifluoromethyl-pyridine hydrochloride (0.371 g, 1.00 mmol) (from Example 1, Step 5) and phenyl 6-cyanopyridin-3-ylcarbamate (0.286 g, 1.00 mmol, prepared according to the procedure described in Synthesis, 1997, 1189-1194 from 3-amino-6-cyanopyridine) in DMSO (2.5 mL) was treated with diisopropylethylamine (0.155 g, 1.2 mmol) and was heated to 50° C. After 3 h, the reaction mixture was partitioned between water and ethyl acetate. The organic layer was separated and the aqueous layer was extracted again with ethyl acetate. The combined organic layer was washed with brine and dried over sodium sulfate, filtered and concentrated to form a residue. The residue was purified by silica gel chromatography (10% of the 1N NH3 in MeOH, in dichloromethane) to provide an oil upon concentration of the pure fractions. This oil was dissolved in 20 mL of diethyl ether and treated with 1 mL of 1N HCl in diethyl ether. The resulting solid was collected by filtration to provide the title compound (270 mg, 56%). MS (APCI 10V) AP+ 480.20; 1H NMR (400 MHz, DMSO-d6) δ ppm 2.36 (t, J=5.46 Hz, 2H) 2.46 (t, J=5.46 Hz, 2H+DMSO) 3.49 (t, J=5.46 Hz, 2H) 3.56 (t, J=5.46 Hz, 2H) 6.39 (s, 1H) 7.03 (m, 2H) 7.12 (d, J=7.80 Hz, 1H) 7.21 (d, J=8.80 Hz, 1H) 7.4 (dd, J=8.5 Hz, 1 Hz, 1H) 7.84 (d, J=8.75 Hz, 1H) 8.10 (dd, J=8.57 Hz, 2.2 Hz, 1H) 8.20 (dd, J=9.24 Hz, 3 Hz, 1H) 8.55 (s, 1H) 8.8 (d, J=2.3 Hz, 1H) 9.29 (s, 1H).

Workup

  1. customthe reaction mixture was partitioned between water and ethyl acetate
  2. customThe organic layer was separated
  3. extractionthe aqueous layer was extracted again with ethyl acetate
  4. washThe combined organic layer was washed with brine
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customto form a residue
  9. customThe residue was purified by silica gel chromatography (10% of the 1N NH3 in MeOH
  10. customin dichloromethane) to provide an oil upon concentration of the pure fractions
  11. filtrationThe resulting solid was collected by filtration

Sources & evidence

ORD record
ord-a0afab7cb2fd4bd4ae73680e31e11499
Source dataset
uspto-grants-2011_10
Patent number
US08044052B2

Reaction notes

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