3-Chloro-5-[(5-chloro-3,6-difluoro-2-pyridinyl)oxy]benzonitrile → HCID 178509961, compound

HRID 1952337Notes

Reaction equation

[Cl:1][C:2]1[CH:3]=[C:4]([CH:7]=[C:8]([O:10][C:11]2[C:16]([F:17])=[CH:15][C:14]([Cl:18])=[C:13](F)[N:12]=2)[CH:9]=1)[C:5]#[N:6].[NH2:20][CH2:21][C:22]1[C:30]2[C:25](=[N:26][CH:27]=[CH:28][CH:29]=2)[NH:24][N:23]=1>CN1C(=O)CCC1.O>[Cl:1][C:2]1[CH:3]=[C:4]([CH:7]=[C:8]([O:10][C:11]2[C:16]([F:17])=[CH:15][C:14]([Cl:18])=[C:13]([NH:20][CH2:21][C:22]3[C:30]4[C:25](=[N:26][CH:27]=[CH:28][CH:29]=4)[NH:24][N:23]=3)[N:12]=2)[CH:9]=1)[C:5]#[N:6]

Participants

Conditions

Temperature: 90 °C

Procedure

A solution of 50 mg (0.166 mmol) of 1-6 and 25 mg (0.166 mmol) of 1-3 in 1.5 mL of dry NMP was heated with stirring at 90° C. under nitrogen. After 7 hours, the reaction was stopped and cooled. The reaction mixture was diluted with water, and extracted twice with EtOAc. The combined EtOAc extracts were washed with water and brine, dried, filtered, and concentrated in vacuo to give a crude oil. The crude product was purified by reversed phase preparative HPLC on a Gilson apparatus to give the title product as a white amorphous solid. MS M+1=430. 1H NMR (CDCl3): 4.77 (d, 2H), 5.60 (br m, 1H), 7.17 (q, 1H), 7.34 (m, 1H), 7.36 (m, 1H), 7.39 (m, 1H), 7.50 (d, 1H), 8.01 (dd, 1H), 8.53 (m, 1H), 10.5-11.5 (br, 1H).

Workup

temperaturecooled
extractionextracted twice with EtOAc
washThe combined EtOAc extracts were washed with water and brine
customdried
filtrationfiltered
concentrationconcentrated in vacuo
customto give a crude oil
customThe crude product was purified by reversed phase preparative HPLC on a Gilson apparatus

Sources & evidence

ORD record: ord-247f4a4a37dd41c881a7cdfe06cfa521
Source dataset: uspto-grants-2013_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08404856B2

Reaction notes

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