Sodium hydride → Methyl 6-[2-anilino-1-(anilinocarbonyl)-2-oxoethyl]nicotinate

HRID 1694833Notes

Reaction equation

[H-].[Na+].[CH:3]1[CH:8]=[CH:7][C:6]([NH:9][C:10]([CH2:12][C:13]([NH:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)=[O:14])=[O:11])=[CH:5][CH:4]=1.F[C:23]1[CH:32]=[CH:31][C:26]([C:27]([O:29][CH3:30])=[O:28])=[CH:25][N:24]=1>CN(C=O)C.C(Cl)Cl.O>[NH:9]([C:10](=[O:11])[CH:12]([C:23]1[CH:32]=[CH:31][C:26]([C:27]([O:29][CH3:30])=[O:28])=[CH:25][N:24]=1)[C:13]([NH:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)=[O:14])[C:6]1[CH:5]=[CH:4][CH:3]=[CH:8][CH:7]=1

Participants

Conditions

Temperature: 100 °C

Procedure

To a suspension of NaH (32 mg, 60% wt. dispersion in mineral oil, 0.80 mmol) in DMF (0.5 mL) at room temperature was added malondianilide (169 mg, 0.67 mmol). The solution was stirred for 20 min and a solution of methyl 6-fluoronicotinate (129 mg, 0.62 mmol) in DMF (1 mL) was added. The reaction mixture was heated to 100° C. for 1 h, cooled to room temperature, and diluted with CH2Cl2 and water. The aqueous phase was extracted with CH2Cl2 (3×) and the combined extracts were washed with brine (1×), dried over MgSO4, filtered, and concentrated. Purification by reverse phase HPLC (40% to 90% MeCN in water) gave methyl 6-[2-anilino-1-(anilinocarbonyl)-2-oxoethyl]nicotinate (66 mg, TFA salt, 21%) as a white solid: ESIMS calcd 390.1 (M++H), found 390.1 (M++H).

Workup

temperaturecooled to room temperature
extractionThe aqueous phase was extracted with CH2Cl2 (3×)
washthe combined extracts were washed with brine (1×)
dry with materialdried over MgSO4
filtrationfiltered
concentrationconcentrated
customPurification by reverse phase HPLC (40% to 90% MeCN in water)

Sources & evidence

ORD record: ord-764f4a98c46546319261f2cb7544e7b8
Source dataset: uspto-grants-2012_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08158825B2

Reaction notes

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