Methanamine, N-methoxy-, hydrochloride (1:1) → N-Methoxy-N-methyl-5-phenylethynylnicotinamide

HRID 606782Notes

Reaction equation

HRID 606782 reaction equation
Cl.CN(C)CCCN=C=NCC.C(N(C(C)C)CC)(C)C.[C:22]1([C:28]#[C:29][C:30]2[CH:31]=[N:32][CH:33]=[C:34]([CH:38]=2)[C:35](O)=[O:36])[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1.Cl.[CH3:40][NH:41][O:42][CH3:43]>O1CCCC1>[CH3:43][O:42][N:41]([CH3:40])[C:35](=[O:36])[C:34]1[CH:38]=[C:30]([C:29]#[C:28][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[CH:31]=[N:32][CH:33]=1

Participants

6

Reactant 4

HCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27792365-(2-Phenyleth-1-Ynyl)Nicotinic Acid

Product 1

HCID 86076555N-Methoxy-N-methyl-5-phenylethynylnicotinamideYield 67.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Add 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride (EDCI) (3.86 g, 20.2 mmol) and diisopropylethylamine (7.0 mL, 40.3 mmol) to a suspension of 5-phenylethynylnicotinic acid (3.0 g, 13.4 mmol) and N,O-dimethylhydroxylamine hydrochloride (1.97 g, 20.2 mmol) in tetrahydrofuran (100 mL) and stir at room temperature overnight. Concentrate the reaction mixture, dissolve the residue in ethyl acetate and wash sequentially with an aqueous solution of phosphate buffer (pH=7) and a saturated aqueous solution of sodium chloride. Dry the organic layer over magnesium sulfate, filter and concentrate. Purify the residue by silica gel chromatography, eluting with 50:50 ethyl acetate:hexanes, to give the title compound as a pale yellow solid (2.4 g, 67%).

Workup

  1. concentrationConcentrate the reaction mixture
  2. dissolutiondissolve the residue in ethyl acetate
  3. washwash sequentially with an aqueous solution of phosphate buffer (pH=7)
  4. dry with materialDry the organic layer over magnesium sulfate
  5. filtrationfilter
  6. concentrationconcentrate
  7. customPurify the residue by silica gel chromatography
  8. washeluting with 50:50 ethyl acetate

Sources & evidence

ORD record
ord-574b67331aa44b678327efa6415698f6
Source dataset
uspto-grants-2011_03
Patent number
US07915424B2

Reaction notes

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