Dimethylformamide → 5-(2,5-dimethyl-1H-pyrrol-1-yl)-4-(4-methylpiperazin-1-yl)nicotinaldehyde

HRID 524898Notes

Reaction equation

Br[C:2]1[CH:3]=[N:4][CH:5]=[C:6]([N:15]2[C:19]([CH3:20])=[CH:18][CH:17]=[C:16]2[CH3:21])[C:7]=1[N:8]1[CH2:13][CH2:12][N:11]([CH3:14])[CH2:10][CH2:9]1.[Li]C(C)(C)C.CN([CH:30]=[O:31])C>C1COCC1>[CH3:21][C:16]1[N:15]([C:6]2[CH:5]=[N:4][CH:3]=[C:2]([C:7]=2[N:8]2[CH2:13][CH2:12][N:11]([CH3:14])[CH2:10][CH2:9]2)[CH:30]=[O:31])[C:19]([CH3:20])=[CH:18][CH:17]=1

Participants

Conditions

Temperature: -78 °C

Procedure

A solution of 1-[3-bromo-5-(2,5-dimethylpyrrol-1-yl)-4-pyridyl]-4-methyl-piperazine (1250 mg, 3.579 mmol) in THF (35.79 mL) was cooled to −78° C. and t-BuLi (2.105 mL of 1.7 M, 3.579 mmol) was added dropwise. The mixture was stirred for 30 mins at −78° C. before DMF (261.6 mg, 277.1 μL, 3.579 mmol) was added dropwise. The mixture was stirred for 2 h at −78° C. The reaction was quenched with MeOH (5 mL) and allowed to warm to room temperature. The reaction was washed with an aqueous saturated solution of ammonium chloride (50 mL) and extracted with EtOAc (100 mL and 50 mL). The combined organics were dried (MgSO4) and evaporated to leave an orange oil. Purification by column chromatography (EtOAc to EtOAc:MeOH 20%) yielded 5-(2,5-dimethyl-1H-pyrrol-1-yl)-4-(4-methylpiperazin-1-yl)nicotinaldehyde as a pale yellow crystalline solid. MS (ES+) 299.2.

Workup

additionwas added dropwise
customThe reaction was quenched with MeOH (5 mL)
temperatureto warm to room temperature
washThe reaction was washed with an aqueous saturated solution of ammonium chloride (50 mL)
extractionextracted with EtOAc (100 mL and 50 mL)
dry with materialThe combined organics were dried (MgSO4)
customevaporated
customto leave an orange oil
customPurification by column chromatography (EtOAc to EtOAc:MeOH 20%)

Sources & evidence

ORD record: ord-3754b9cfa27d44769a0708e1dafb9ee9
Source dataset: uspto-grants-2016_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09340546B2

Reaction notes

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