2-Methoxyethylamine → 2-(4-Bromo-3-[1,3]dioxolan-2-yl-phenoxy)-6-(2-methoxy-ethylamino)-nicotinonitrile

HRID 1471537Notes

Reaction equation

BrC1C=CC(OC2C=CC(C#N)=C(Cl)N=2)=CC=1C1OCCO1.BrC1C=CC(OC2C=CC(C#N)=C(Cl)N=2)=CC=1C1OCCO1.[Br:45][C:46]1[CH:61]=[CH:60][C:49]([O:50][C:51]2[N:58]=[C:57](Cl)[CH:56]=[CH:55][C:52]=2[C:53]#[N:54])=[CH:48][C:47]=1[CH:62]1[O:66][CH2:65][CH2:64][O:63]1.[CH3:67][O:68][CH2:69][CH2:70][NH2:71]>C(#N)C>[Br:45][C:46]1[CH:61]=[CH:60][C:49]([O:50][C:51]2[N:58]=[C:57]([NH:71][CH2:70][CH2:69][O:68][CH3:67])[CH:56]=[CH:55][C:52]=2[C:53]#[N:54])=[CH:48][C:47]=1[CH:62]1[O:66][CH2:65][CH2:64][O:63]1

Participants

Conditions

Temperature: 80 °C

Procedure

To a solution of compound mixture, 6-(4-bromo-3-[1,3]dioxolan-2-yl-phenoxy)-2-chloro-nicotinonitrile and 2-(4-bromo-3-[1,3]dioxolan-2-yl-phenoxy)-6-chloro-nicotinonitrile (4+5, 2.5 g, 6.6 mmol) in acetonitrile (anhydrous, 50 mL) was added 2-methoxy-ethylamine (5.7 mL, 66 mmol). The reaction was heated at 80° C. for 2 hours. After the reaction, all volatile components were evaporated under vacuum. Purification was achieved by silica gel chromatography, eluting with 10%-80% EtOAc/hexanes gradient, affording 1.0 g (36% yield) of the title compound. 1H NMR (400 MHz, chloroform-d) δ ppm 7.58-7.47 (m, 2 H), 7.41 (d, J=3.1 Hz, 1 H), 7.04 (dd, J=8.6, 2.7 Hz, 1 H), 6.09-6.03 (m, 2 H), 5.37 (t, J=5.1 Hz, 1 H), 4.14-3.99 (m, 4 H), 3.37 (t, J=5.1 Hz, 2 H), 3.31-3.23 (m, 5 H).

Workup

customAfter the reaction
customall volatile components were evaporated under vacuum
customPurification
washeluting with 10%-80% EtOAc/hexanes gradient

Sources & evidence

ORD record: ord-14ce0cae249a49d48ed2931dd87db2c7
Source dataset: uspto-grants-2015_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09012431B2

Reaction notes

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