4-Ethylbenzoyl chloride → 4-Ethyl-N-[[2-[(3S)-3-methyl-2,6-dioxopiperidin-3-YL]-1,3-dioxoisoindolin-5-YL]methyl]benzamide

HRID 63410

Reaction equation

HRID 63410 reaction equation
[CH2:1]([C:3]1[CH:11]=[CH:10][C:6]([C:7](Cl)=[O:8])=[CH:5][CH:4]=1)[CH3:2].Cl.[NH2:13][CH2:14][C:15]1[CH:16]=[C:17]2[C:21](=[CH:22][CH:23]=1)[C:20](=[O:24])[N:19]([C@@:25]1([CH3:33])[CH2:30][CH2:29][C:28](=[O:31])[NH:27][C:26]1=[O:32])[C:18]2=[O:34]>C(#N)C>[CH2:1]([C:3]1[CH:11]=[CH:10][C:6]([C:7]([NH:13][CH2:14][C:15]2[CH:16]=[C:17]3[C:21](=[CH:22][CH:23]=2)[C:20](=[O:24])[N:19]([C@@:25]2([CH3:33])[CH2:30][CH2:29][C:28](=[O:31])[NH:27][C:26]2=[O:32])[C:18]3=[O:34])=[O:8])=[CH:5][CH:4]=1)[CH3:2]

Participants

4

Reactant 2

HCID 853684-Ethylbenzoyl chlorideHCID 670196915-aminomethyl-2-[(3S)-3-methyl-2,6-dioxo-piperidin-3-yl]-isoindole-1,3-dione hydrochloride

Product 1

HCID 247883104-Ethyl-N-[[2-[(3S)-3-methyl-2,6-dioxopiperidin-3-YL]-1,3-dioxoisoindolin-5-YL]methyl]benzamideYield 76%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent2×

Procedure

TEA (0.44 g, 4.4 mmol) was added to a mixture of 4-ethylbenzoyl chloride (0.34 g, 2.0 mmol) and 5-aminomethyl-2-[(3S)-3-methyl-2,6-dioxo-piperidin-3-yl]-isoindole-1,3-dione hydrochloride (0.67 g, 2.0 mmol) in acetonitrile (20 mL). The mixture was stirred at room temperature for 2 hours, and was evaporated under vacuum. The residue was partitioned between water (100 mL) and ethyl acetate (100 mL), and the organic phase was evaporated. The residue was chromatographed on silica gel using ethyl acetate as the mobile phase, providing 0.65 g, in 76% yield. The product was obtained as a white solid; mp 160-162° C.; HPLC, Waters Symmetry C-18, 3.9×150 mm, 5 μm, 1 mL/min, 240 nm, 45/55 CH3CN/0.1% H3PO4, 4.20 (97.47%); 1H NMR (DMSO-d6) δ 1.19 (t, J=7.7 Hz, 3H), 1.89 (s, 3H), 2.02-2.08 (m, 1H), 2.54-2.62 (m, 2H), 2.65-2.78 (m, 3H), 4.61 (d, J=6.0 Hz, 2H), 7.32 (d, J=8.1 Hz, 2H), 7.76-7.84 (m, 5H), 9.14 (t, J=6.0 Hz, 1H), 11.01 (s, 1H); 13C NMR (DMSO-d6) δ 15.4, 21.1, 28.1, 28.6, 29.2, 42.6, 58.8, 121.6, 123.2, 127.4, 127.8, 129.6, 131.4, 131.5, 133.4, 147.6, 147.7, 166.4, 167.8, 167.9, 172.2, 172.3; Anal. Calcd for C24H23N3O5: C, 66.50; H, 5.35; N, 9.69. Found: C, 66.30; H, 5.26; N, 9.56.

Workup

  1. customwas evaporated under vacuum
  2. customThe residue was partitioned between water (100 mL) and ethyl acetate (100 mL)
  3. customthe organic phase was evaporated
  4. customThe residue was chromatographed on silica gel
  5. customproviding 0.65 g
  6. customThe product was obtained as a white solid

Sources & evidence

ORD record
ord-789f6bf65453443cb1c0b667ddc694ae
Source dataset
uspto-grants-2016_09
Patent number
US09447070B2

Linked notes

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