4-Cyanobenzohydrazide → 4-Cyano-benzoic acid N'-[2-(3-chloro-4-cyano-2-vinyl-phenylamino)-3-hydroxy-butyryl]-hydrazide

HRID 2388560Notes

Reaction equation

HRID 2388560 reaction equation
[Cl:1][C:2]1[C:3]([CH:18]=[CH2:19])=[C:4]([NH:10][CH:11]([CH:15]([OH:17])[CH3:16])[C:12]([OH:14])=O)[CH:5]=[CH:6][C:7]=1[C:8]#[N:9].[C:20]([C:22]1[CH:31]=[CH:30][C:25]([C:26]([NH:28][NH2:29])=[O:27])=[CH:24][CH:23]=1)#[N:21].OC1C2N=NNC=2C=CC=1.Cl.CN(C)CCCN=C=NCC>C1COCC1>[Cl:1][C:2]1[C:3]([CH:18]=[CH2:19])=[C:4]([NH:10][CH:11]([CH:15]([OH:17])[CH3:16])[C:12]([NH:29][NH:28][C:26](=[O:27])[C:25]2[CH:24]=[CH:23][C:22]([C:20]#[N:21])=[CH:31][CH:30]=2)=[O:14])[CH:5]=[CH:6][C:7]=1[C:8]#[N:9]

Participants

6

Reactant 4

HCID 4567324-CyanobenzohydrazideHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 670060332-(3-Chloro-4-cyano-2-vinyl-phenylamino)-3-hydroxy-butyric acidHCID 178418300HCID 178418300, compound

Product 1

HCID 670060504-Cyano-benzoic acid N'-[2-(3-chloro-4-cyano-2-vinyl-phenylamino)-3-hydroxy-butyryl]-hydrazideYield 49%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-15 °C

Procedure

2-(3-Chloro-4-cyano-2-vinyl-phenylamino)-3-hydroxy-butyric acid (690 mg, 3.8 mmol) and 4-cyanobenzohydrazide (673 mg, 4.18 mmol) were mixed together in THF (100 ml) and cooled to −15° C. under N2 atmosphere. To the pre-cooled reaction mixture were added hydroxybenzotriazole (HOBT) (514 mg, 3.8 mmol), TEA (0.8 mL, 5.7 mmol) followed by N-(3-Dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (EDCI) (1.09 g, 5.7 mmol). The reaction mixture was allowed to stir at −20° C. for 20 min and then at room temperature overnight. After the reaction was complete based on TLC, the urea was filtered off and the solution was washed with 5% citric acid (2×60 mL), 5% NaHCO3 (2×60 mL) followed by water (60 mL) and then dried (Na2SO4) to provide the crude product as a yellow solid (0.79 g, 49%): 1H NMR (400 MHz, d6-acetone, δ in ppm) 9.92 (br s, 1H), 9.49 (br s, 1H), 7.99 (d, J=9 Hz, 2H), 7.81 (d, J=9 Hz, 2H), 7.42 (d, J=9 Hz, 1H), 6.61 (d, J=9 Hz, 1H), 6.53 (dd, J=12 and 18 Hz), 5.99 (d, J=9 Hz, 1H), 5.73 (dd, J=2 and 12 Hz, 2H), 5.64 (dd, J=2 and 18 Hz), 4.29-4.22 (m, 1H), 4.01-3.99 (m, 1H) and 1.20 (d, J=7 Hz, 3H).

Workup

  1. customTo the pre-cooled reaction mixture
  2. customat room temperature
  3. customovernight
  4. filtrationthe urea was filtered off
  5. washthe solution was washed with 5% citric acid (2×60 mL), 5% NaHCO3 (2×60 mL)
  6. dry with materialdried (Na2SO4)

Sources & evidence

ORD record
ord-4af165e0717c4c6ab70f62176e734875
Source dataset
uspto-grants-2012_09
Patent number
US08268872B2

Reaction notes

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