Chloroacetaldehyde → Methyl 7-(4-bromo-2-chlorophenylamino)-8-chloroimidazo[1,2-a]pyridine-6-carboxylate

HRID 558211Notes

Reaction equation

[NH2:1][C:2]1[C:11]([Cl:12])=[C:10]([NH:13][C:14]2[CH:19]=[CH:18][C:17]([Br:20])=[CH:16][C:15]=2[Cl:21])[C:5]([C:6]([O:8][CH3:9])=[O:7])=[CH:4][N:3]=1.Cl[CH2:23][CH:24]=O>CN(C=O)C>[Br:20][C:17]1[CH:18]=[CH:19][C:14]([NH:13][C:10]2[C:5]([C:6]([O:8][CH3:9])=[O:7])=[CH:4][N:3]3[CH:23]=[CH:24][N:1]=[C:2]3[C:11]=2[Cl:12])=[C:15]([Cl:21])[CH:16]=1

Participants

Conditions

Temperature: 80 °C

Procedure

To a suspension of methyl 6-amino-4-(4-bromo-2-chlorophenylamino)-5-chloronicotinate (966 mg, 2.48 mmol) in 13 ml DMF was added chloroacetaldehyde (50% aq. solution, 0.32 ml, 396 mg, 2.52 mmol) and the mixture was heated in a closed vessel to 80° C. for 3 h. The dark solution was cooled to room temperature and the DMF was removed by vacuum distillation. The residue was dissolved in THF and directly purified by column chromatography (EtOAc/hexanes 10:1+2% TEA) which delivered the desired product (638 mg, 62%). Rf (EtOAc/Hexanes 10:1)=0.4. 1H-NMR (500 MHz, MeOH-D3): δ=9.16 (s, 1H), 7.86-7.85 (d, 1H), 7.54-7.53 (d, 1H), 7.50-7.48 (d, 1H), 7.19-7.17 (dd, 1H), 6.51-6.50 (d, 1H), 3.82 (s, 3H).

Workup

temperatureThe dark solution was cooled to room temperature
customthe DMF was removed by vacuum distillation
dissolutionThe residue was dissolved in THF
customdirectly purified by column chromatography (EtOAc/hexanes 10:1+2% TEA) which

Sources & evidence

ORD record: ord-e40d9f5c9f5e457ca3aa0eefb5f2824e
Source dataset: uspto-grants-2011_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08063049B2

Reaction notes

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