Semicarbazide hydrochloride → 2-(4-{(3E)-4-{2-[(4-tert-Butylbenzyl)oxy]phenyl}-2-[2-(4-cyanophenyl)ethyl]but-3-en-1-yl}-benzoyl)hydrazinecarboxamide

HRID 1672690Notes

Reaction equation

HRID 1672690 reaction equation
C(Cl)(=O)C(Cl)=O.[C:7]([C:11]1[CH:47]=[CH:46][C:14]([CH2:15][O:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=2/[CH:23]=[CH:24]/[CH:25]([CH2:36][CH2:37][C:38]2[CH:43]=[CH:42][C:41]([C:44]#[N:45])=[CH:40][CH:39]=2)[CH2:26][C:27]2[CH:35]=[CH:34][C:30]([C:31](O)=[O:32])=[CH:29][CH:28]=2)=[CH:13][CH:12]=1)([CH3:10])([CH3:9])[CH3:8].Cl.[NH2:49][NH:50][C:51]([NH2:53])=[O:52].[OH-].[Na+]>C1(C)C=CC=CC=1.CN(C=O)C.C1COCC1.O>[C:7]([C:11]1[CH:47]=[CH:46][C:14]([CH2:15][O:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=2/[CH:23]=[CH:24]/[CH:25]([CH2:36][CH2:37][C:38]2[CH:43]=[CH:42][C:41]([C:44]#[N:45])=[CH:40][CH:39]=2)[CH2:26][C:27]2[CH:28]=[CH:29][C:30]([C:31]([NH:49][NH:50][C:51]([NH2:53])=[O:52])=[O:32])=[CH:34][CH:35]=2)=[CH:13][CH:12]=1)([CH3:10])([CH3:8])[CH3:9]

Participants

9

Reactant 4

HCID 11236Semicarbazide hydrochlorideHCID 14798Sodium HydroxideHCID 65578Oxalyl chlorideHCID 578644144-{(3E)-4-{2-[(4-tert-Butylbenzyl)oxy]phenyl}-2-[2-(4-cyanophenyl)ethyl]but-3-en-1-yl}benzoic acid

Product 1

HCID 578643832-(4-{(3E)-4-{2-[(4-tert-Butylbenzyl)oxy]phenyl}-2-[2-(4-cyanophenyl)ethyl]but-3-en-1-yl}-benzoyl)hydrazinecarboxamide

Reagents, catalysts & solvents 4

HCID 6228DimethylformamideCatalystHCID 962WaterSolventHCID 1140TolueneSolventHCID 8028TetrahydrofuranSolvent

Procedure

836 mg (6.62 mmol) of oxalyl chloride are slowly added dropwise to a solution of 600 mg (1.10 mmol) of 4-{(3E)-4-{2-[(4-tert-butylbenzyl)oxy]phenyl}-2-[2-(4-cyanophenyl)ethyl]but-3-en-1-yl}benzoic acid from Example 105A in 6 ml of dry toluene with 4 drops of DMF while cooling in ice. The reaction mixture is stirred at RT for 10 minutes and then heated to reflux for 1 hour. After cooling, the mixture is concentrated in vacuo, and the residue is coevaporated twice with toluene and then taken up in 6 ml of THF. This solution is added dropwise to a previously prepared solution of 135.4 mg (1.21 mmol) of semicarbazide hydrochloride and 88.3 mg (2.21 mmol) of sodium hydroxide in 1 ml of THF and 0.25 ml of water at 0° C. The mixture is stirred at 0° C. for 2 hours and then at RT for 30 minutes, and the residue after concentration is reacted without further purification in the next stage.

Workup

  1. temperaturewhile cooling in ice
  2. temperatureheated
  3. temperatureto reflux for 1 hour
  4. temperatureAfter cooling
  5. concentrationthe mixture is concentrated in vacuo
  6. stirringThe mixture is stirred at 0° C. for 2 hours
  7. waitat RT for 30 minutes
  8. concentrationthe residue after concentration
  9. customis reacted without further purification in the next stage

Sources & evidence

ORD record
ord-9b9bb33a55394dc9a6af9258c39a79e9
Source dataset
uspto-grants-2011_08
Patent number
US07998988B2

Reaction notes

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