Diethyl Ether → Methyl 4-cyano-2-(2-(isoquinolin-5-yl)acetamido)thiophene-3-carboxylate

HRID 1519784Notes

Reaction equation

Br[C:2]1[C:3]([C:21]([O:23][CH3:24])=[O:22])=[C:4]([NH:7][C:8](=[O:20])[CH2:9][C:10]2[CH:19]=[CH:18][CH:17]=[C:16]3[C:11]=2[CH:12]=[CH:13][N:14]=[CH:15]3)[S:5][CH:6]=1.[C:25]([Cu])#[N:26].[NH4+].[OH-].C(OCC)C>CN(C=O)C>[C:25]([C:2]1[C:3]([C:21]([O:23][CH3:24])=[O:22])=[C:4]([NH:7][C:8](=[O:20])[CH2:9][C:10]2[CH:19]=[CH:18][CH:17]=[C:16]3[C:11]=2[CH:12]=[CH:13][N:14]=[CH:15]3)[S:5][CH:6]=1)#[N:26]

Participants

Conditions

Temperature: 100 °C

Procedure

To a stirring mixture of methyl 4-bromo-2-(2-(isoquinolin-5-yl)acetamido)thiophene-3-carboxylate (100 mg) in DMF (0.5 mL) was added CuCN (150 mg). The resulting mixture was heated to 100° C. overnight. The reaction mixture was cooled to room temperature. To this mixture was added a 10% NH4OH solution and ethyl ether. The crude mixture was stirred at rt for 1 h. A normal aqueous workup with ethyl ether was followed. The organic layers were dried over MgSO4, filtered and concentrated under reduce pressure. The crude product mixture was purified by silica gel column chromatography to give methyl 4-cyano-2-(2-(isoquinolin-5-yl)acetamido)thiophene-3-carboxylate. Method[1], MS(ESI) 352.0 [M+H], Retention time=1.343 min.

Workup

temperatureThe reaction mixture was cooled to room temperature
dry with materialThe organic layers were dried over MgSO4
filtrationfiltered
concentrationconcentrated
customThe crude product mixture was purified by silica gel column chromatography

Sources & evidence

ORD record: ord-ed37f8da7ded4a6fab3d590fdf39ab19
Source dataset: uspto-grants-2015_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09073891B2

Reaction notes

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