Acetohydrazide → 5-ethyl-6-methoxy-2-methyl-nicotinic acid N'-acetyl-hydrazide

HRID 1921353Notes

Reaction equation

HRID 1921353 reaction equation
[CH2:1]([C:3]1[C:4]([O:13][CH3:14])=[N:5][C:6]([CH3:12])=[C:7]([CH:11]=1)[C:8]([OH:10])=O)[CH3:2].F[B-](F)(F)F.O=C1C=CC=CN1OC(N(C)C)=[N+](C)C.O.OC1C2N=NNC=2C=CC=1.[C:46]([NH:49][NH2:50])(=[O:48])[CH3:47].C(N(C(C)C)C(C)C)C>ClCCl.O>[C:46]([NH:49][NH:50][C:8](=[O:10])[C:7]1[CH:11]=[C:3]([CH2:1][CH3:2])[C:4]([O:13][CH3:14])=[N:5][C:6]=1[CH3:12])(=[O:48])[CH3:47]

Participants

8

Reactant 5

HCID 14039AcetohydrazideHCID 81531DiisopropylethylamineHCID 2733204O-(2-Oxo-1(2H)-pyridyl)-N,N,N',N'-tetramethyluronium TetrafluoroborateHCID 674920765-Ethyl-6-methoxy-2-methyl-nicotinic acidHCID 178526939HCID 178526939, compound

Product 1

HCID 674924785-ethyl-6-methoxy-2-methyl-nicotinic acid N'-acetyl-hydrazideYield 143.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

Under a nitrogen atmosphere in a round bottom flask, 5-ethyl-6-methoxy-2-methyl-nicotinic acid (500 mg, 2.56 mmol) of Step 2, Example 14 is dissolved in dichloromethane (30 mL). O-(1,2-dihydro-2-oxo-1-pyridyl)-N,N,N′,N′-tetramethyluronium tetrafluoroborate (990 mg, 3.33 mmol) is added, followed by hydroxybenzotriazole hydrate (510 mg, 3.33 mmol). The resulting mixture is stirred at rt for 45 min to give a suspension, which is treated with acetic hydrazide (285 mg, 3.85 mmol) followed by N-ethyl-diisopropylamine (1.16 mL, 6.66 mmol). The resulting solution is stirred at rt for 32 hr, LC/MS shows the reaction to be complete. The reaction is diluted with water and the mixture is extracted with six portions of dichloromethane, the combined extract is dried over magnesium sulfate, filtered and evaporated. The crude product is purified by flash chromatography on a 10-gram silica gel cartridge by elution with dichloromethane:ethyl acetate (1:1, increasing to 1:2). Fractions containing the product are combined and evaporated to obtain 5-ethyl-6-methoxy-2-methyl-nicotinic acid N′-acetylhydrazide (give 923 mg) as a white solid. MS: m/e=252 (M+H); 1H NMR (300 MHz, CDCl3, δ, ppm): 8.72 (1H, d), 8.50 (1H, d), 7.49 (1H, s), 3.96 (3H, s), 2.59 (3H, s), 2.54 (2H, q), 2.12 (3H, s), 1.17 (3H, t).

Workup

  1. customto give a suspension, which
  2. stirringThe resulting solution is stirred at rt for 32 hr
  3. customthe reaction
  4. extractionthe mixture is extracted with six portions of dichloromethane
  5. extractionthe combined extract
  6. dry with materialis dried over magnesium sulfate
  7. filtrationfiltered
  8. customevaporated
  9. customThe crude product is purified by flash chromatography on a 10-gram silica gel cartridge by elution with dichloromethane:ethyl acetate (1:1, increasing to 1:2)
  10. additionFractions containing the product
  11. customevaporated

Sources & evidence

ORD record
ord-6fcc341e15104986b7f675dc40de5bf5
Source dataset
uspto-grants-2012_05
Patent number
US08173682B2

Reaction notes

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