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

HRID 1036112Notes

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-aad90d207a67466898fc7d2387594cb3
Source dataset: uspto-grants-2013_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08546403B2

Reaction notes

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