Triethylamine → n-[5-Tert-butyl-3-[(2r)-tetrahydrofuran-2-ylmethyl]-1,3-oxazol-2(3h)-ylidene]-5-chloro-2-methoxybenzamide

HRID 717235Notes

Reaction equation

HRID 717235 reaction equation
[C:1]([C:5]1[O:9][C:8](=[NH:10])[N:7]([CH2:11][C@H:12]2[CH2:16][CH2:15][CH2:14][O:13]2)[CH:6]=1)([CH3:4])([CH3:3])[CH3:2].CCN=C=NCCCN(C)C.Cl.ON1C2C=CC=CC=2N=N1.C(N(CC)CC)C.[Cl:46][C:47]1[CH:48]=[CH:49][C:50]([O:56][CH3:57])=[C:51]([CH:55]=1)[C:52](O)=[O:53]>O1CCCC1.C(OCC)(=O)C>[C:1]([C:5]1[O:9][C:8](=[N:10][C:52](=[O:53])[C:51]2[CH:55]=[C:47]([Cl:46])[CH:48]=[CH:49][C:50]=2[O:56][CH3:57])[N:7]([CH2:11][C@H:12]2[CH2:16][CH2:15][CH2:14][O:13]2)[CH:6]=1)([CH3:4])([CH3:2])[CH3:3]

Participants

8

Reactant 5

HCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 769705-Chloro-o-anisic acidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 66643286(r)-5-Tert-butyl-3-((tetrahydrofuran-2-yl)methyl)oxazol-2(3h)-imine

Product 1

HCID 25262919n-[5-Tert-butyl-3-[(2r)-tetrahydrofuran-2-ylmethyl]-1,3-oxazol-2(3h)-ylidene]-5-chloro-2-methoxybenzamide

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of Example 13B (1.24 g, 5.53 mmol) in tetrahydrofuran (10 mL) was added N-(3-dimethylaminopropyl)-N-ethylcarbodiimide hydrochloride (1.06 g, 5.53 mmol), 1-hydroxybenzotriazole (0.85 g, 5.55 mmol), triethylamine (0.45 mL, 3.2 mmol) and 5-chloro-2-methoxybenzoic acid (Aldrich) (1.03 g, 5.55 mmol). The mixture was stirred at 80° C. overnight, cooled to room temperature, diluted with ethyl acetate, washed with 1 M aqueous NaHCO3, dried (Na2SO4), filtered and concentrated. The residue was purified by column chromatography using an Analogix® Intelliflash280™ (SiO2, 0-50% ethyl acetate in hexanes) to provide the title product. MS (ESI+) m/z 393 (M+H)+; 1H NMR (300 MHz, CDCl3) δ ppm 1.20 (s, 9H), 1.59-1.71 (m, 1H), 1.83-1.97 (m, 2H), 2.02-2.14 (m, 1H), 3.66 (dd, J=14.2, 7.5 Hz, 1H), 3.75-3.82 (m, 1H), 3.82 (s, 3H), 3.82-3.92 (m, 1H), 4.07 (dd, J=14.2, 2.7 Hz, 1H), 4.13-4.24 (m, 1H), 6.52 (s, 1H), 6.83 (d, J=8.8 Hz, 1H), 7.27 (dd, J=9.0, 2.7 Hz, 1H), 7.74 (d, J=2.7 Hz, 1H).

Workup

  1. temperaturecooled to room temperature
  2. washwashed with 1 M aqueous NaHCO3
  3. dry with materialdried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was purified by column chromatography

Sources & evidence

ORD record
ord-006c3d27d1ec4c1e8f08c68e2ef95f83
Source dataset
uspto-grants-2015_11
Patent number
US09193713B2

Reaction notes

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