4-Methylmorpholine → 2-(3-(4-fluorobenzyl)-2-oxoimidazolidin-1-yl)-N-methylisonicotinamide

HRID 714351Notes

Reaction equation

HRID 714351 reaction equation
[F:1][C:2]1[CH:23]=[CH:22][C:5]([CH2:6][N:7]2[CH2:11][CH2:10][N:9]([C:12]3[CH:13]=[C:14]([CH:18]=[CH:19][N:20]=3)[C:15]([OH:17])=O)[C:8]2=[O:21])=[CH:4][CH:3]=1.[CH3:24][N:25]1CCOCC1.ClC(OCC(C)C)=O.Cl.CN>O1CCCC1>[F:1][C:2]1[CH:23]=[CH:22][C:5]([CH2:6][N:7]2[CH2:11][CH2:10][N:9]([C:12]3[CH:13]=[C:14]([CH:18]=[CH:19][N:20]=3)[C:15]([NH:25][CH3:24])=[O:17])[C:8]2=[O:21])=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 79724-Methylmorpholine2×HCID 62365Isobutyl chloroformateHCID 6364545Methylamine hydrochlorideHCID 582477912-(3-(4-Fluorobenzyl)-2-oxoimidazolidin-1-yl)isonicotinic acid

Product 1

HCID 445551432-(3-(4-fluorobenzyl)-2-oxoimidazolidin-1-yl)-N-methylisonicotinamideYield 43.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 2-(3-(4-fluorobenzyl)-2-oxoimidazolidin-1-yl)isonicotinic acid (0.18 g, 0.56 mmol) and 4-methylmorpholine (0.12 g, 1.18 mmol) in anhydrous tetrahydrofuran (15 mL) was added isobutyl chloroformate (0.10 g, 0.69 mmol) at 0° C. The resulting solution was stirred at ambient temperature for 3 hours, followed by the addition of methylamine hydrochloride (0.08 g, 1.12 mmol) and 4-methylmorpholine (0.06 g, 0.56 mmol) at 0° C. The reaction mixture was stirred for 17 hours and concentrated in vacuo. The residue was purified by column chromatography to give 2-(3-(4-fluorobenzyl)-2-oxoimidazolidin-1-yl)-N-methylisonicotinamide as a colorless solid (0.08 g, 43%): mp 118-120° C.; 1H NMR (300 MHz, CDCl3) δ 8.54 (s, 1H), 8.36-8.34 (m, 1H), 7.40-7.37 (m, 1H), 7.29-7.24 (m, 2H), 7.06-6.99 (m, 2H), 6.47 (br s, 1H), 4.44 (s, 2H), 4.07-4.01 (m, 2H), 3.40-3.35 (m, 2H), 2.98 (d, J=4.8 Hz, 3H); 13C NMR (75 MHz, CDCl3) δ 166.5, 153.0, 148.4, 143.1, 132.1, 129.9, 129.8, 116.1, 115.9, 115.6, 108.8, 47.3, 41.3, 41.0, 26.8; MS (ES+) m/z 329.2 (M+1).

Workup

  1. stirringThe reaction mixture was stirred for 17 hours
  2. concentrationconcentrated in vacuo
  3. customThe residue was purified by column chromatography

Sources & evidence

ORD record
ord-883b388e5d944331a59d5f2a18d18a89
Source dataset
uspto-grants-2015_11
Patent number
US09187426B2

Reaction notes

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