Hydrochloric Acid → 4-(Aminomethyl)-2-[1-(3-ethoxy-4-methoxyphenyl)-2-(methylsulfonyl)ethyl]isoindoline-1,3-dione hydrochloride

HRID 2244516Notes

Reaction equation

HRID 2244516 reaction equation
[C:1]([C:3]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:4]=1[C:5](=[O:30])[N:6]([CH:13]([C:19]1[CH:24]=[CH:23][C:22]([O:25][CH3:26])=[C:21]([O:27][CH2:28][CH3:29])[CH:20]=1)[CH2:14][S:15]([CH3:18])(=[O:17])=[O:16])[C:7]2=[O:12])#[N:2].[H][H].O.[ClH:34]>CO.C(O)C.[Pd]>[ClH:34].[NH2:2][CH2:1][C:3]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:4]=1[C:5](=[O:30])[N:6]([CH:13]([C:19]1[CH:24]=[CH:23][C:22]([O:25][CH3:26])=[C:21]([O:27][CH2:28][CH3:29])[CH:20]=1)[CH2:14][S:15]([CH3:18])(=[O:17])=[O:16])[C:7]2=[O:12]

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 962WaterHCID 187583844-Cyano-2-[1-(3-ethoxy-4-methoxyphenyl)-2-methylsulfonyl-ethyl]isoindoline-1,3-dioneHCID 178418361HCID 178418361, compound

Product 1

HCID 116699694-(Aminomethyl)-2-[1-(3-ethoxy-4-methoxyphenyl)-2-(methylsulfonyl)ethyl]isoindoline-1,3-dione hydrochlorideYield 80%

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 702EthanolSolventHCID 887MethanolSolvent

Procedure

A mixture of 4-cyano-2-[1-(3-ethoxy-4-methoxyphenyl)-2-methylsulfonyl-ethyl]isoindoline-1,3-dione (0.5 g, 1.17 mmol) and 10% Pd/C (0.15 g) in 4 N hydrochloric acid (1 mL) and methanol (40 mL) was hydrogenated in Parr Shaker apparatus under 50 psi of hydrogen overnight. To the resulting slurry was added water (2 mL) to dissolve the product. The reaction mixture was then filtered through Celite and the filtrate was concentrated in vacuo. The residue was slurried in ethyl acetate (10 mL) to afford 0.52 g of the crude product. The product was reslurried in hot ethanol (15 mL) to afford 4-(aminomethyl)-2-[1-(3-ethoxy-4-methoxyphenyl)-2-methylsulfonylethyl]isoindoline-1,3-dione hydrochloride (0.44 g, 80% yield): mp 237-239° C.; 1H NMR (DMSO-d6) δ 8.79 (s, 3H, Ar), 8.04-7.89 (m, 3H, Ar), 7.11-6.91 (m, 3H, Ar), 5.83-5.77 (dd, J=4.2, 10.1 Hz, 1H, NCH), 4.49-4.47 (m, 2H, CH2), 4.41-4.31 (m, 1H, CHH), 4.21-4.13 (m, 1H, CHH), 4.04 (q, J=6.8 Hz, 2H, CH2), 3.73 (s. 3H, CH3), 3.64 (s, 3H, CH3), 1.32 (t, J=6.8 Hz, 3H, CH3); 13C NMR (DMSO-d6) δ 167.48, 166.93, 148.95, 147.87, 135.39, 134.71, 132.82, 131.32, 129.50, 128.30, 123.34, 119.89, 112.55, 111.79, 63.87, 55.52, 53.07, 47.46, 41.08, 36.84, 14.66; Anal. Calcd for C21H25N2O6SCl: C, 53.79; H, 5.37; N, 5.97; S, 6.84; Cl, 7.56. Found: C, 53.49, H, 5.47; N, 5.75; S, 6.61; Cl, 7.51.

Workup

  1. dissolutionto dissolve the product
  2. filtrationThe reaction mixture was then filtered through Celite
  3. concentrationthe filtrate was concentrated in vacuo
  4. customto afford 0.52 g of the crude product

Sources & evidence

ORD record
ord-46cc28f55ce646c1a47b2af9017c4856
Source dataset
uspto-grants-2010_03
Patent number
US07678825B2

Reaction notes

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