Acetic Acid → 5-((5-(2-Methoxy-6-((4-methoxybenzyl)oxy)phenyl)-1H-pyrazol-3-yl)amino)pyrazine-2-carbonitrile

HRID 1878314Notes

Reaction equation

HRID 1878314 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[C:5]([O:9][CH2:10][C:11]2[CH:16]=[CH:15][C:14]([O:17][CH3:18])=[CH:13][CH:12]=2)[C:4]=1[C:19](=O)/[CH:20]=[C:21](\[NH:24][C:25]1[N:26]=[CH:27][C:28]([C:31]#[N:32])=[N:29][CH:30]=1)/SC.O.[NH2:35][NH2:36].C(O)(=O)C>C(O)C>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[C:5]([O:9][CH2:10][C:11]2[CH:16]=[CH:15][C:14]([O:17][CH3:18])=[CH:13][CH:12]=2)[C:4]=1[C:19]1[NH:36][N:35]=[C:21]([NH:24][C:25]2[N:26]=[CH:27][C:28]([C:31]#[N:32])=[N:29][CH:30]=2)[CH:20]=1

Participants

5

Reactant 3

HCID 176Acetic AcidHCID 24654Hydrazine hydrate (1:1)HCID 58305822(E)-5-(3-(2-Methoxy-6-(4-methoxybenzyloxy)phenyl)-1-(methylthio)-3-oxoprop-1-enylamino)pyrazine-2-carbonitrile

Product 1

HCID 672336865-((5-(2-Methoxy-6-((4-methoxybenzyl)oxy)phenyl)-1H-pyrazol-3-yl)amino)pyrazine-2-carbonitrileYield 87%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
65 °C

Procedure

A 10 L flange-neck flask, equipped with an air stirrer rod and paddle, thermometer, water condenser, and nitrogen bubbler, is charged with (E)-5-(3-(2-methoxy-6-(4-methoxybenzyloxy)phenyl)-1-(methylthio)-3-oxoprop-1-enylamino)pyrazine-2-carbonitrile (196 g, 423.8 mmol) and absolute ethanol (3 L). To the stirred suspension under nitrogen is added hydrazine hydrate (41.0 mL, 838.7 mmol) and glacial acetic acid (66.0 mL, 1.15 moles). A small exotherm is noted. The yellow suspension is warmed up to 65° C. Heating is then discontinued and the reaction mixture is allowed to cool to room temperature. The mixture is allowed to stand overnight under a nitrogen atmosphere. The solid is collected by filtration, washed with fresh ethanol, and dried in vacuo at 45° C. to give 140 g (87% yield for two steps) of a bright yellow solid. The product is used in the next step without further purification. LC-ES/MS m/z 429.2 [M+H]+.

Workup

  1. customA 10 L flange-neck flask, equipped with an air stirrer rod and paddle
  2. temperatureHeating
  3. temperatureto cool to room temperature
  4. filtrationThe solid is collected by filtration
  5. washwashed with fresh ethanol
  6. customdried in vacuo at 45° C.
  7. customto give 140 g (87% yield for two steps) of a bright yellow solid
  8. customThe product is used in the next step without further purification

Sources & evidence

ORD record
ord-8f6e9ddec64e438eaa8135a4e90eca11
Source dataset
uspto-grants-2012_11
Patent number
US08314108B2

Reaction notes

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