2-tert-Butyl-1,3-diisopropylisourea → 4-(4-Bromo-2-chlorophenylamino)-6-chloronicotinic acid tert-butyl ester

HRID 494710

Reaction equation

HRID 494710 reaction equation
[C:1](OC(=NC(C)C)NC(C)C)([CH3:4])([CH3:3])[CH3:2].Cl.[Br:16][C:17]1[CH:22]=[CH:21][C:20]([NH:23][C:24]2[C:29]([C:30]([OH:32])=[O:31])=[CH:28][N:27]=[C:26]([Cl:33])[CH:25]=2)=[C:19]([Cl:34])[CH:18]=1>C1COCC1.CCOC(C)=O>[C:1]([O:31][C:30](=[O:32])[C:29]1[C:24]([NH:23][C:20]2[CH:21]=[CH:22][C:17]([Br:16])=[CH:18][C:19]=2[Cl:34])=[CH:25][C:26]([Cl:33])=[N:27][CH:28]=1)([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 2

HCID 110417822-tert-Butyl-1,3-diisopropylisoureaHCID 865967774-(4-Bromo-2-chlorophenylamino)-6-chloronicotinic acid hydrochloride salt

Product 1

HCID 865967784-(4-Bromo-2-chlorophenylamino)-6-chloronicotinic acid tert-butyl esterYield 107.3%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

2-tert-Butyl-1,3-diisopropylisourea (8.04 g, 40.1 mmol) was added to a mixture of 4-(4-bromo-2-chlorophenylamino)-6-chloronicotinic acid hydrochloride salt (24) (2.91 g, 7.31 mmol) in THF (165 mL). After stirring for 2 hours at room temperature and 30 minutes at reflux, the reaction mixture was cooled to room temperature and diluted with EtOAc. The organic layer was washed with 10% K2CO3 and brine, dried (Na2SO4) and concentrated. The resulting residue was dissolved in CH2Cl2 and filtered. The filtrate was concentrated and purified by flash column chromatography using the Biotage system (CH2Cl2) to give the desired product (40) (3.28 g, 78%).

Workup

  1. temperatureat reflux
  2. temperaturethe reaction mixture was cooled to room temperature
  3. washThe organic layer was washed with 10% K2CO3 and brine
  4. dry with materialdried (Na2SO4)
  5. concentrationconcentrated
  6. dissolutionThe resulting residue was dissolved in CH2Cl2
  7. filtrationfiltered
  8. concentrationThe filtrate was concentrated
  9. custompurified by flash column chromatography

Sources & evidence

ORD record
ord-b9925329c8134f9fbab4bddce9e963e1
Source dataset
uspto-grants-2009_05
Patent number
US07538120B2

Linked notes

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