Diisopropylethylamine → Methyl 6-amino-5-((3-(3-methylfuran-2-carboxamido)phenyl)ethynyl)nicotinate

HRID 1099678Notes

Reaction equation

[C:1]([C:3]1[CH:4]=[C:5]([NH:9][C:10]([C:12]2[O:13][CH:14]=[CH:15][C:16]=2[CH3:17])=[O:11])[CH:6]=[CH:7][CH:8]=1)#[CH:2].[NH2:18][C:19]1[C:28](I)=[CH:27][C:22]([C:23]([O:25][CH3:26])=[O:24])=[CH:21][N:20]=1.CCN(C(C)C)C(C)C>CN(C=O)C.CCOC(C)=O.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cu]I>[CH3:26][O:25][C:23](=[O:24])[C:22]1[CH:27]=[C:28]([C:2]#[C:1][C:3]2[CH:8]=[CH:7][CH:6]=[C:5]([NH:9][C:10]([C:12]3[O:13][CH:14]=[CH:15][C:16]=3[CH3:17])=[O:11])[CH:4]=2)[C:19]([NH2:18])=[N:20][CH:21]=1

Participants

Conditions

Temperature: 50 °C

Procedure

In a 4 mL vial, N-(3-ethynylphenyl)-3-methylfuran-2-carboxamide (0.607 g, 2.70 mmol) and methyl 6-amino-5-iodonicotinate (0.5 g, 1.80 mmol) were dissolved in DMF (6 mL). The solution was degassed by bubbling N2(g) through it for ˜30 min. To the degassed solution was added DIPEA (1.25 mL, 7.19 mmol), followed by Pd(PPh3)2Cl2 (0.126 g, 0.18 mmol) and CuI (0.068 g, 0.360 mmol). The reaction mixture was allowed to stir at 50° C. for 3 h. The reaction mixture then was taken up in EtOAc (10 mL) and was extracted with brine (3×10 mL). The organic layers were combined and concentrated in vacuo. The crude mixture was purified via column chromatography (gradient eluant mixture of EtOAc in Hexanes: 25% to 100% EtOAc) to give the title compound as a white solid (0.554 g, 82%).

Workup

customThe solution was degassed
customby bubbling N2(g) through it for ˜30 min
extractionwas extracted with brine (3×10 mL)
concentrationconcentrated in vacuo
customThe crude mixture was purified via column chromatography (gradient eluant mixture of EtOAc in Hexanes: 25% to 100% EtOAc)

Sources & evidence

ORD record: ord-aa7d3ba95fed472fa0bde55c0f656fc0
Source dataset: uspto-grants-2012_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08143410B2

Reaction notes

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