Diisopropylethylamine → N-(5-(2,2-difluoro-6-methylbenzo[d][1,3]dioxol-5-yl)pyrazin-2-yl)-2,6-difluorobenzamide

HRID 2272205Notes

Reaction equation

[F:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]([F:11])[C:3]=1[C:4](Cl)=[O:5].[F:12][C:13]1([F:30])[O:17][C:16]2[CH:18]=[C:19]([CH3:29])[C:20]([C:22]3[N:23]=[CH:24][C:25]([NH2:28])=[N:26][CH:27]=3)=[CH:21][C:15]=2[O:14]1.CCN(C(C)C)C(C)C>ClCCl.O1CCCC1.CO.[OH-].[Na+]>[F:30][C:13]1([F:12])[O:17][C:16]2[CH:18]=[C:19]([CH3:29])[C:20]([C:22]3[N:23]=[CH:24][C:25]([NH:28][C:4](=[O:5])[C:3]4[C:2]([F:1])=[CH:10][CH:9]=[CH:8][C:7]=4[F:11])=[N:26][CH:27]=3)=[CH:21][C:15]=2[O:14]1

Participants

Conditions

Temperature: 60 °C

Procedure

Under an atmosphere of argon, 2,6-difluorobenzoyl chloride (40 mg, 0.2 mmol) was added to a stirred solution of 9 (30 mg, 0.1 mmol) and Hünig's base (120 μL, 88 mg, 0.7 mmol) in dichloromethane (1.0 mL) at room temperature. The reaction was stirred for 0.5 h. The solution was diluted with tetrahydrofuran (0.9 mL), methanol (0.6 mL) and 2 M sodium hydroxide solution (0.2 mL). The mixture was stirred and heated to 60° C. for 10 min then cooled to room temperature, extracted with dichloromethane (3×5 mL), dried with sodium sulfate and concentrated under reduced pressure. Flash chromatography (ISCO system, silica, 0-20% ethyl acetate in hexane) provided 10 (26.4 mg, 58%) as a crystalline solid: LRESIMS m/z 406.1 [M+H]+, calcd. for C19H12F4N3O3 406.1.

Workup

stirringThe mixture was stirred
temperaturethen cooled to room temperature
extractionextracted with dichloromethane (3×5 mL)
dry with materialdried with sodium sulfate
concentrationconcentrated under reduced pressure

Sources & evidence

ORD record: ord-c99543ffc5c3496d8f3828d886a94350
Source dataset: uspto-grants-2015_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09120751B2

Reaction notes

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