Diisopropylethylamine → 2-(3-(4-fluorobenzyl)-2-oxoimidazolidin-1-yl)-N-(oxazol-4-ylmethyl)isonicotinamide

HRID 714352Notes

Reaction equation

HRID 714352 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](O)=[O:16])[C:8]2=[O:21])=[CH:4][CH:3]=1.C(N(C(C)C)CC)(C)C.O.ON1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.[O:56]1[CH:60]=[C:59]([CH2:61][NH2:62])[N:58]=[CH:57]1>CN(C)C=O>[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:62][CH2:61][C:59]3[N:58]=[CH:57][O:56][CH:60]=3)=[O:16])[C:8]2=[O:21])=[CH:4][CH:3]=1

Participants

7

Reactant 5

HCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 230556901,3-Oxazol-4-ylmethanamineHCID 582477912-(3-(4-Fluorobenzyl)-2-oxoimidazolidin-1-yl)isonicotinic acid

Product 1

HCID 445553022-(3-(4-fluorobenzyl)-2-oxoimidazolidin-1-yl)-N-(oxazol-4-ylmethyl)isonicotinamideYield 49%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of 2-(3-(4-fluorobenzyl)-2-oxoimidazolidin-1-yl)isonicotinic acid (0.35 g, 1.11 mmol), diisopropylethylamine (0.86 g, 6.66 mmol), 1-hydroxybenzotriazole monohydrate (0.39 g, 2.89 mmol) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (0.28 g, 1.44 mmol) in anhydrous N,N-dimethylformamide (10.0 mL) was stirred at ambient temperature for 10 minutes, followed by the addition of oxazol-4-ylmethanamine (0.23 g, 1.67 mmol). The resulting reaction mixture was stirred at ambient temperature for 17 hours and concentrated in vacuo. The residue was dissolved in ethyl acetate (60 mL), washed with saturated aqueous sodium bicarbonate (10 mL) solution, water (2×10 mL) and brine (10 mL). The organic solution was dried over anhydrous sodium sulphate, filtered and concentrated in vacuo. The residue was purified by column chromatography to give 2-(3-(4-fluorobenzyl)-2-oxoimidazolidin-1-yl)-N-(oxazol-4-ylmethyl)isonicotinamide as a colorless solid (0.21 g, 49%): mp 197-199° C.; 1H NMR (300 MHz, DMSO-d6) δ 9.15 (t, J=5.6 Hz, 1H), 8.65 (s, 1H), 8.37-8.30 (m, 2H), 7.95 (s, 1H), 7.35-7.06 (m, 5H), 4.49-4.33 (m, 4H), 3.93 (t, J=8.0 Hz, 2H), 3.37-3.25 (m, 2H); 13C NMR (75 MHz, DMSO-d6) δ 165.6, 163.6, 160.4, 156.8, 153.5, 152.5, 148.4, 143.3, 137.8, 136.6, 133.6, 133.6, 130.4, 130.3, 116.0, 115.7, 115.2, 110.5, 46.6, 41.6, 35.7; MS (ES+) m/z 396.3 (M+1).

Workup

  1. customThe resulting reaction mixture
  2. concentrationconcentrated in vacuo
  3. dissolutionThe residue was dissolved in ethyl acetate (60 mL)
  4. washwashed with saturated aqueous sodium bicarbonate (10 mL) solution, water (2×10 mL) and brine (10 mL)
  5. dry with materialThe organic solution was dried over anhydrous sodium sulphate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by column chromatography

Sources & evidence

ORD record
ord-d24f7177178f41d289a4d8453d731519
Source dataset
uspto-grants-2015_11
Patent number
US09187426B2

Reaction notes

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