Diisopropylethylamine → 2,6-difluoro-N-(5-(6-methoxy-2,3-dihydro-1H-inden-5-yl)pyridin-2-yl)benzamide

HRID 874639Notes

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].[CH3:12][O:13][C:14]1[CH:22]=[C:21]2[C:17]([CH2:18][CH2:19][CH2:20]2)=[CH:16][C:15]=1[C:23]1[CH:24]=[CH:25][C:26]([NH2:29])=[N:27][CH:28]=1.CCN(C(C)C)C(C)C>ClCCl.O1CCCC1.CO.[OH-].[Na+]>[F:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]([F:11])[C:3]=1[C:4]([NH:29][C:26]1[CH:25]=[CH:24][C:23]([C:15]2[CH:16]=[C:17]3[C:21](=[CH:22][C:14]=2[O:13][CH3:12])[CH2:20][CH2:19][CH2:18]3)=[CH:28][N:27]=1)=[O:5]

Participants

Conditions

Temperature: 60 °C

Procedure

Under an atmosphere of argon, 2,6-difluorobenzoyl chloride (44 mg, 0.2 mmol) was added to a stirred solution of 126 (30 mg, 0.1 mmol) and Hünig's base (130 μL, 97 mg, 0.7 mmol) in dichloromethane (0.7 mL) at room temperature. The reaction was stirred for 0.5 h. The solution was diluted with tetrahydrofuran (0.6 mL), methanol (0.4 mL) and 2 M sodium hydroxide solution (0.2 mL). The mixture was stirred and heated to 60° C. for 60 min then cooled to room temperature, diluted with dichloromethane (5 mL), dried with sodium sulfate and concentrated under reduced pressure. Flash chromatography (ISCO system, silica, 0-20% ethyl acetate in hexane) provided 127 (14.4 mg, 30%) as a solid: LRESIMS m/z 381.1 [M+H]+, calcd. for C22H19F2N2O2 381.1.

Workup

stirringThe mixture was stirred
temperaturethen cooled to room temperature
dry with materialdried with sodium sulfate
concentrationconcentrated under reduced pressure

Sources & evidence

ORD record: ord-192bd01769fc4296a1a1907e3a5c6c7e
Source dataset: uspto-grants-2015_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08980629B2

Reaction notes

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