Hydrazine hydrate (1:1) → 4-(4-Bromo-2-chlorophenylamino)-5-chloro-6-hydrazinonicotinic acid ethyl ester

HRID 494720Notes

Reaction equation

HRID 494720 reaction equation
BrC1C=CC(NC2C(C(O)=O)=CN=C(Cl)C=2Cl)=C(Cl)C=1.O.[NH2:22][NH2:23].[CH2:24]([O:26][C:27](=[O:45])[C:28]1[C:33]([NH:34][C:35]2[CH:40]=[CH:39][C:38]([Br:41])=[CH:37][C:36]=2[Cl:42])=[C:32]([Cl:43])[C:31]([Cl:44])=[N:30][CH:29]=1)[CH3:25]>CN(C)C(=O)C.CCOC(C)=O>[CH2:24]([O:26][C:27](=[O:45])[C:28]1[C:33]([NH:34][C:35]2[CH:40]=[CH:39][C:38]([Br:41])=[CH:37][C:36]=2[Cl:42])=[C:32]([Cl:43])[C:31]([Cl:44])=[N:30][CH:29]=1)[CH3:25].[CH2:24]([O:26][C:27](=[O:45])[C:28]1[C:33]([NH:34][C:35]2[CH:40]=[CH:39][C:38]([Br:41])=[CH:37][C:36]=2[Cl:42])=[C:32]([Cl:43])[C:31]([NH:22][NH2:23])=[N:30][CH:29]=1)[CH3:25]

Participants

7

Reactant 3

HCID 24654Hydrazine hydrate (1:1)HCID 116612174-(4-Bromo-2-chlorophenylamino)-5,6-dichloronicotinic acidHCID 865967804-(4-Bromo-2-chlorophenylamino)-5,6-dichloronicotinic acid ethyl ester

Product 2

HCID 688607444-(4-Bromo-2-chlorophenylamino)-5-chloro-6-hydrazinonicotinic acid ethyl esterYield 36.1%HCID 865967804-(4-Bromo-2-chlorophenylamino)-5,6-dichloronicotinic acid ethyl ester

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 31374DimethylacetamideSolvent

Conditions

Temperature
90 °C

Procedure

4-(4-Bromo-2-chlorophenylamino)-5,6-dichloronicotinic acid ethyl ester (48) was prepared by standard methods from 4-(4-bromo-2-chlorophenylamino)-5,6-dichloronicotinic acid. Hydrazine monohydrate (0.59 mL, 12.16 mmol) was added to a solution of 4-(4-bromo-2-chlorophenylamino)-5,6-dichloronicotinic acid ethyl ester (48) (1.72 g, 4.05 mmol) in N,N-dimethylacetamide (20 mL). After stirring at 90° C. for 1 hour, the reaction mixture was cooled to room temperature and diluted with EtOAc. The organic layer was washed with water and brine, dried (Na2SO4) and concentrated. Purification by flash column chromatography using the Biotage system (20:1 CH2Cl2:EtOAc) provided the desired product (49) (307 mg, 18%).

Workup

  1. temperaturethe reaction mixture was cooled to room temperature
  2. washThe organic layer was washed with water and brine
  3. dry with materialdried (Na2SO4)
  4. concentrationconcentrated
  5. customPurification by flash column chromatography

Sources & evidence

ORD record
ord-2d68f9f8f54f43499adbdb56306d7533
Source dataset
uspto-grants-2009_05
Patent number
US07538120B2

Reaction notes

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