Nicotinic Acid → HCID 21981146, compound

HRID 901889Notes

Reaction equation

HRID 901889 reaction equation
C(Cl)(=O)C(Cl)=O.[C:7]([OH:15])(=O)[C:8]1[CH:13]=[CH:12][CH:11]=[N:10][CH:9]=1.[S-:16][C:17]#[N:18].[NH4+].[O:20]([C:27]1[CH:28]=[C:29]([CH:31]=[CH:32][CH:33]=1)[NH2:30])[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1>C(Cl)Cl.CN(C=O)C.CC(C)=O>[O:20]([C:27]1[CH:28]=[C:29]([NH:30][C:17]([NH:18][C:7]([C:8]2[CH:9]=[N:10][CH:11]=[CH:12][CH:13]=2)=[O:15])=[S:16])[CH:31]=[CH:32][CH:33]=1)[C:21]1[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=1

Participants

8

Reactant 4

HCID 938Nicotinic AcidHCID 15666Ammonium thiocyanateHCID 65578Oxalyl chlorideHCID 771353-Phenoxyaniline

Product 1

HCID 21981146HCID 21981146, compound

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideCatalystHCID 180AcetoneSolventHCID 6344DichloromethaneSolvent

Procedure

Oxalyl chloride (2.8 mL, 32 mmol) is added to a suspension of nicotinic acid (3.7 g, 30 mmol) in methylene chloride (35 ml) followed by 2 drops of DMF. The reaction is refluxed for 1.5 h and all the volatiles are removed on a rotovap. Alternatively, rather than convert nicotinic acid to the acid chloride, commercially available nicotinyl chloride hydrochloride may be used. The solid is resuspended in methylene chloride/acetone (1:1) (50 ml) and an acetone (10 ml) solution of ammonium thiocyanate (3.5 g, 45 mmol) is added. The reaction is stirred for 1 h at room temperature followed by the addition of 3-phenoxy aniline. The stirring is continued over night at room temperature. The solvent is evaporated and the residue suspended in water (100 ml) and extracted with methylene chloride (3×75 ml). The organic layers are combined, dried over sodium sulphate, filtered to remove any insoluble materials and evaporated. The residue is purified by column chromatography on silica gel and crystallized from methanol to give the desired product. MP: 144.5-145.5° C., 1H NMR (300 MHz, DMSO): δ 12.330 (s, 1H), 11.93 (s, 1H), 9.07 (s, 1H), 8.80 (m, 1H), 8.300 (d, 2H, J=8.1 Hz), 7.955 (s, 1H), 7.81 (d, 1H, J=9.0 Hz), 7.57 (m, 1H), 7.299 (d, 1H, J=9.0 Hz), 4.13 (t, 2H, J=6.2 Hz), 1.77-1.72 (m, 2H,), 1.44-1.34 (m, 4H), 0.92-0.87 (t, 3H, J=7.1). MS (APCI) m/z 350.1 [M+H]+.

Workup

  1. temperatureThe reaction is refluxed for 1.5 h
  2. customall the volatiles are removed on a rotovap
  3. waitThe stirring is continued over night at room temperature
  4. customThe solvent is evaporated
  5. extractionextracted with methylene chloride (3×75 ml)
  6. dry with materialdried over sodium sulphate
  7. filtrationfiltered
  8. customto remove any insoluble materials
  9. customevaporated
  10. customThe residue is purified by column chromatography on silica gel
  11. customcrystallized from methanol

Sources & evidence

ORD record
ord-70827833fdd94ded8c9e965b47881665
Source dataset
uspto-grants-2008_04
Patent number
US07365068B2

Reaction notes

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