Ammonium Chloride → mGluR2 antagonist 1

HRID 922758Notes

Reaction equation

[O:1]=[C:2]1[CH2:6][CH2:5][C:4](=[O:7])[N:3]1[CH2:8][C:9]1[CH:18]=[C:17]2[C:12]([C:13]([C:21]3[CH:26]=[CH:25][C:24]([F:27])=[CH:23][CH:22]=3)=[CH:14][C:15]([C:19]#[N:20])=[N:16]2)=[CH:11][CH:10]=1.C([O-])([O-])=[O:29].C([O-])([O-])=O.OO.OO.OO.[Na+].[Na+].[Na+].[Na+].[NH4+].[Cl-]>CC(C)=O.O>[O:7]=[C:4]1[CH2:5][CH2:6][C:2](=[O:1])[N:3]1[CH2:8][C:9]1[CH:18]=[C:17]2[C:12]([C:13]([C:21]3[CH:22]=[CH:23][C:24]([F:27])=[CH:25][CH:26]=3)=[CH:14][C:15]([C:19]([NH2:20])=[O:29])=[N:16]2)=[CH:11][CH:10]=1

Participants

Conditions

Temperature: 50 °C

Procedure

7-[(2,5-Dioxopyrrolidin-1-yl)methyl]-4-(4-fluorophenyl)quinoline-2-carbonitrile (2-6, 12.8 g, 35.5 mmol, 1.0 equiv.) was dissolved in acetone (473 mL)/water (237 mL) and sodium percarbonate (55.7 g, 178 mmol, 5.0 equiv) was added. The resulting mixture was stirred at 50° C. for 1.5 hours. The mixture was cooled and poured over aqueous NH4Cl (saturated, 250 mL), extracted with ethyl acetate (3×200 mL), dried over Na2SO4, filtered and concentrated to afford 7-[(2,5-dioxopyrrolidin-1-yl)methyl]-4-(4-fluorophenyl)quinoline-2-carboxamide (2-7, 5.5 g, 41% over 3 steps) as a colorless solid. 1H NMR (400 MHz, CDCl3): δ 8.216 (s, 1H); 8.156 (s, 1H); 8.091 (br s, 1H); 7.908 (d, J=8.69 Hz, 1H); 7.614 (dd, J1=8.79 Hz, J2=1.71 Hz, 1H); 7.470-7.498 (m, 2H); 7.211-7.262 (m, 2H); 5.668 (br s, 1H); 4.902 (s, 2H); 2.776 (s, 4H). LRMS m/z (M+H)+ 378.3 found, 378.1 required.

Workup

additionwas added
temperatureThe mixture was cooled
extractionextracted with ethyl acetate (3×200 mL)
dry with materialdried over Na2SO4
filtrationfiltered
concentrationconcentrated

Sources & evidence

ORD record: ord-a9e5f22a52d442069ec149a16c1c013e
Source dataset: uspto-grants-2016_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09278960B2

Reaction notes

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