Dimethylformamide → 6-Chloro-8-(4-ethoxyphenylamino)imidazo[1,2-b]pyridazine-3-carbonitrile

HRID 2239861Notes

Reaction equation

Br[C:2]1[N:6]2[N:7]=[C:8]([Cl:21])[CH:9]=[C:10]([NH:11][C:12]3[CH:17]=[CH:16][C:15]([O:18][CH2:19][CH3:20])=[CH:14][CH:13]=3)[C:5]2=[N:4][CH:3]=1.[CH3:22][N:23](C=O)C>C(OCC)(=O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[C-]#N.[C-]#N.[Zn+2]>[Cl:21][C:8]1[CH:9]=[C:10]([NH:11][C:12]2[CH:17]=[CH:16][C:15]([O:18][CH2:19][CH3:20])=[CH:14][CH:13]=2)[C:5]2[N:6]([C:2]([C:22]#[N:23])=[CH:3][N:4]=2)[N:7]=1

Participants

Conditions

Temperature: 200 °C

Procedure

In a 5 ml microwave vial was added 3-bromo-6-chloro-N-(4-ethoxyphenyl)imidazo[1,2-b]pyridazin-8-amine (0.3 g, 0.8 mmol) from 1b, Pd(PPh3)4 (0.18 g, 0.16 mmol), Zn(CN)2 (0.47 g, 4.0 mmol) and DMF (3 ml). The reaction was heated via microwave for 25 min at 200° C. Upon cooling, the reaction mixture was diluted with ethyl acetate and filtered through a plug of celite. The solvent was removed in vacuo and the resulting material was purified by silica gel chromatography (ethyl acetate/heptane, 25 min gradient: 5-50% ethyl acetate) to give 0.11 g of 6-chloro-8-(4-ethoxyphenylamino)imidazo[1,2-b]pyridazine-3-carbonitrile.

Workup

temperatureUpon cooling
filtrationfiltered through a plug of celite
customThe solvent was removed in vacuo
customthe resulting material was purified by silica gel chromatography (ethyl acetate/heptane, 25 min gradient: 5-50% ethyl acetate)

Sources & evidence

ORD record: ord-cf2c04b5d9c04ea5854760e253efdbee
Source dataset: uspto-grants-2010_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07723336B2

Reaction notes

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