Trifluoroacetic acid → 1-(4-Chloro-phenyl)-6-(4-iodo-phenyl)-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c)pyridine-3-carboxylic acid methyl ester

HRID 860831Notes

Reaction equation

[CH3:1][O:2][C:3]([C:5]1[CH:13]2[C:8](N3CCOCC3)([C:9](=[O:21])[N:10]([C:14]3[CH:19]=[CH:18][C:17]([I:20])=[CH:16][CH:15]=3)[CH2:11][CH2:12]2)[N:7]([C:28]2[CH:33]=[CH:32][C:31]([Cl:34])=[CH:30][CH:29]=2)[N:6]=1)=[O:4].FC(F)(F)C(O)=O>C(Cl)Cl>[CH3:1][O:2][C:3]([C:5]1[C:13]2[CH2:12][CH2:11][N:10]([C:14]3[CH:15]=[CH:16][C:17]([I:20])=[CH:18][CH:19]=3)[C:9](=[O:21])[C:8]=2[N:7]([C:28]2[CH:33]=[CH:32][C:31]([Cl:34])=[CH:30][CH:29]=2)[N:6]=1)=[O:4]

Participants

Conditions

Temperature: 25 °C

Procedure

A solution of 1-(4-chloro-phenyl)-6-(4-iodo-phenyl)-7a-morpholin-4-yl-7-oxo-3a,4,5,6,7,7a-hexahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxylic acid methyl ester (52, 595 mg, 1.0 mmol) in methylene chloride (CH2Cl2, 4 mL) was treated with trifluoroacetic acid (TFA, 1.0 mL) at 25° C., and the resulting reaction mixture was stirred at 25° C. for an additional 30 min. When HPLC and TLC showed the reaction was complete, the solvents were removed in vacuo. The residue was directly purified by flash column chromatography (SiO2, 5–20% EtOAc/hexane gradient elution) to afford the desired elimination product (53, 467 mg, 508 mg theoretical, 92%) as a pale-yellow oil, which solidified upon standing at room temperature in vacuo. For 53, CIMS m/z 508/510 (M++H, C20H15ClIN3O3).

Workup

customthe resulting reaction mixture
customthe solvents were removed in vacuo
customThe residue was directly purified by flash column chromatography (SiO2, 5–20% EtOAc/hexane gradient elution)
customto afford the desired elimination product (53, 467 mg, 508 mg theoretical, 92%) as a pale-yellow oil, which
customupon standing at room temperature in vacuo

Sources & evidence

ORD record: ord-054e8fdb5c1846eb817b087f0d28d972
Source dataset: uspto-grants-2006_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07153960B2

Reaction notes

Loading…