3-Chloro-4-fluoroaniline → 4-[4-(3-Chloro-4-fluoro-phenylamino)-7H-pyrrolo[2,3-d]pyrimidin-6-yl]-benzoic acid ethyl ester

HRID 133020Notes

Reaction equation

[CH2:1]([O:3][C:4](=[O:21])[C:5]1[CH:10]=[CH:9][C:8]([C:11]2[NH:20][C:14]3[N:15]=[CH:16][N:17]=[C:18](Cl)[C:13]=3[CH:12]=2)=[CH:7][CH:6]=1)[CH3:2].[Cl:22][C:23]1[CH:24]=[C:25]([CH:27]=[CH:28][C:29]=1[F:30])[NH2:26]>C(O)CCC>[CH2:1]([O:3][C:4](=[O:21])[C:5]1[CH:10]=[CH:9][C:8]([C:11]2[NH:20][C:14]3[N:15]=[CH:16][N:17]=[C:18]([NH:26][C:25]4[CH:27]=[CH:28][C:29]([F:30])=[C:23]([Cl:22])[CH:24]=4)[C:13]=3[CH:12]=2)=[CH:7][CH:6]=1)[CH3:2]

Participants

Conditions

Temperature: 145 °C

Procedure

3.6 g (12 mmol) 4-(4-Chloro-7H-pyrrolo[2,3-d]pyrimidin-6-yl)-benzoic acid ethyl ester (WO 97/02266) are suspended in 80 ml n-butanol and treated with 3.5 g (24 mmol) 3-chloro-4-fluoro-aniline. The mixture is heated to 145° C. under stirring. After 30 min a clear brown solution is obtained which turns into a thick suspension after 2 h. After a total of 3 h the reaction mixture is cooled in an ice bath and the product collected by filtration; m.p.>300° C.; Rf (dichloromethane/ethanol 95:5 plus 1% conc. ammonia)=0.29; HPLC tR=11.66 min.

Workup

customAfter 30 min a clear brown solution is obtained which
temperatureAfter a total of 3 h the reaction mixture is cooled in an ice bath
filtrationthe product collected by filtration

Sources & evidence

ORD record: ord-d036e378e1e747a3849be00ca48aec54
Source dataset: uspto-grants-2008_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07390805B2

Reaction notes

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