3-Pyridinecarboxaldehyde → HCID 11993991, compound

HRID 1913353Notes

Reaction equation

HRID 1913353 reaction equation
[CH:1](=O)[C:2]1[CH:7]=[CH:6][CH:5]=[N:4][CH:3]=1.S([NH:19][NH2:20])(C1C=CC(C)=CC=1)(=O)=O.[OH-].[Na+].[CH2:23]([NH:26][C:27](=[O:33])[O:28][C:29]([CH3:32])([CH3:31])[CH3:30])[C:24]#[CH:25]>CCO.O.CCOC(C)=O>[N:4]1[CH:5]=[CH:6][CH:7]=[C:2]([C:1]2[CH:25]=[C:24]([CH2:23][NH:26][C:27](=[O:33])[O:28][C:29]([CH3:30])([CH3:32])[CH3:31])[NH:20][N:19]=2)[CH:3]=1

Participants

7

Reactant 4

HCID 103713-PyridinecarboxaldehydeHCID 14798Sodium HydroxideHCID 15303P-ToluenesulfonylhydrazideHCID 11073648tert-butyl N-(prop-2-yn-1-yl)carbamate

Product 1

HCID 11993991HCID 11993991, compoundYield 36.2%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 22728543Water ethylacetateSolvent

Procedure

(See FIG. 11.) To a solution of nicotinaldehyde (150 μL, 1.59 mmol) in 95% EtOH (5 mL) was added 2-tosylhydrazine (296 mg, 1.59 mmol) and the resultant solution was stirred at room temperature for 2 h. To the solution was added aqueous sodium hydroxide (5 N, 0.32 mL, 1.59 mmol) and the solution was stirred for 20 min. To the solution was added a solution of tert-butyl prop-2-ynylcarbamate (1.23 g, 7.95 mmol) and the resultant solution was warmed to 50° C. and stirred under an argon atmosphere for 96 h. The solution was poured into a water/EtOAc mixture (1:1, 100 mL), the organic fraction was collected and the aqueous fraction was extracted with EtOAc (2×20 mL). The combined organic fractions were dried (Na2SO4), filtered and the solvent was removed in vacuo. The crude material was chromatographed on silica gel (EtOAc/Hex, 50/50, Rf=0.08) to afford the title compound 31 (158 mg, 36% yield) as a white solid: mp=185-187° C.; 1H NMR. (CDCl3) δ 8.92 (m, 1H), 8.50 (m, 1H), 8.01 (m, 1H), 7.28 (m, 1H), 6.47 (s, 1H); 5.62 (br s, 1H); 4.34 (d, J=6 Hz, 1H), 1.45 (s, 9H); LRMS (ESI) m/z calcd for C14H19N4O2 [M+H]+ 275. found 275.

Workup

  1. stirringstirred under an argon atmosphere for 96 h
  2. customthe organic fraction was collected
  3. extractionthe aqueous fraction was extracted with EtOAc (2×20 mL)
  4. dry with materialThe combined organic fractions were dried (Na2SO4)
  5. filtrationfiltered
  6. customthe solvent was removed in vacuo
  7. customThe crude material was chromatographed on silica gel (EtOAc/Hex, 50/50, Rf=0.08)

Sources & evidence

ORD record
ord-708a976449bc4d85b74c05a063390468
Source dataset
uspto-grants-2013_12
Patent number
US08609708B2

Reaction notes

Loading…