2-tert-Butyl-1,3-diisopropylisourea → 4-(4-Bromo-2-chlorophenylamino)-6-chloronicotinic acid tert-butyl ester
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
Product 1
Reagents, catalysts & solvents 2
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
- temperatureat reflux
- temperaturethe reaction mixture was cooled to room temperature
- washThe organic layer was washed with 10% K2CO3 and brine
- dry with materialdried (Na2SO4)
- concentrationconcentrated
- dissolutionThe resulting residue was dissolved in CH2Cl2
- filtrationfiltered
- concentrationThe filtrate was concentrated
- custompurified by flash column chromatography
Sources & evidence
- ORD record
- ord-88e1d9512abe4273aa28366c6652d074
- Source dataset
- uspto-grants-2006_12
- Patent number
- US07144907B2
Reaction notes
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