p-Toluenesulfonic acid → 1-(2-bromo-pyridin-4-yl)-1H-benzoimidazole-5-carboxylic acid methyl ester

HRID 453064Notes

Reaction equation

[CH3:1][O:2][C:3](=[O:19])[C:4]1[CH:9]=[CH:8][C:7]([NH:10][C:11]2[CH:16]=[CH:15][N:14]=[C:13]([Br:17])[CH:12]=2)=[C:6]([NH2:18])[CH:5]=1.[CH:20](OC)(OC)OC.C1(C)C=CC(S(O)(=O)=O)=CC=1>C1COCC1>[CH3:1][O:2][C:3]([C:4]1[CH:9]=[CH:8][C:7]2[N:10]([C:11]3[CH:16]=[CH:15][N:14]=[C:13]([Br:17])[CH:12]=3)[CH:20]=[N:18][C:6]=2[CH:5]=1)=[O:19]

Participants

Conditions

Temperature: 60 °C

Procedure

3-Amino-4-(2-bromo-pyridin-4-ylamino)-benzoic acid methyl ester 4 (3 g; 9.3 mmol) was dissolved in 50 ml dry THF and added trimethyl orthoformate (1.4 ml; 13.9 mmol) and p-toluenesulphonic acid (1 g), the reaction mixture was heated to 60° C. for 6 h. LCMS showed almost complete conversion and the reaction was quenched with sodium bicarbonate and extracted with EtOAc (500 ml*3). The organic layer was washed with water and brine. Finally it was dried over sodium sulphate and concentrated in vacuo to give the expected product 5. The compound was pure enough for progress into the next step as seen by NMR and HPLC.

Workup

customthe reaction was quenched with sodium bicarbonate
extractionextracted with EtOAc (500 ml*3)
washThe organic layer was washed with water and brine
dry with materialFinally it was dried over sodium sulphate
concentrationconcentrated in vacuo

Sources & evidence

ORD record: ord-da172db2096d4939ba61493dbfbbdb92
Source dataset: uspto-grants-2013_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08492408B2

Reaction notes

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