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

HRID 391589Notes

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

customwas 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-e3c46647a9db499b8887af1df3e2a169
Source dataset: uspto-grants-2013_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08383825B2

Reaction notes

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