(S)-2-(1-(3-ethoxy-4-methoxyphenyl)-2-(methylsulfonyl)ethyl)-7-nitroisoindolin-1-one → (S)-7-amino-2-(1-(3-ethoxy-4-methoxyphenyl)-2-(methylsulfonyl)ethyl)isoindolin-1-one

HRID 1019521Notes

Reaction equation

HRID 1019521 reaction equation
[CH2:1]([O:3][C:4]1[CH:5]=[C:6]([C@H:12]([N:18]2[CH2:26][C:25]3[C:20](=[C:21]([N+:27]([O-])=O)[CH:22]=[CH:23][CH:24]=3)[C:19]2=[O:30])[CH2:13][S:14]([CH3:17])(=[O:16])=[O:15])[CH:7]=[CH:8][C:9]=1[O:10][CH3:11])[CH3:2]>CO.C(OCC)(=O)C.CO.[Pd]>[NH2:27][C:21]1[CH:22]=[CH:23][CH:24]=[C:25]2[C:20]=1[C:19](=[O:30])[N:18]([C@@H:12]([C:6]1[CH:7]=[CH:8][C:9]([O:10][CH3:11])=[C:4]([O:3][CH2:1][CH3:2])[CH:5]=1)[CH2:13][S:14]([CH3:17])(=[O:15])=[O:16])[CH2:26]2

Participants

5

Reactant 1

HCID 58224189(S)-2-(1-(3-ethoxy-4-methoxyphenyl)-2-(methylsulfonyl)ethyl)-7-nitroisoindolin-1-one

Product 1

HCID 66718531(S)-7-amino-2-(1-(3-ethoxy-4-methoxyphenyl)-2-(methylsulfonyl)ethyl)isoindolin-1-oneYield 55%

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 887MethanolSolventHCID 21584119Ethylacetate methanolSolvent

Procedure

A suspension of 2-[(1S)-1-(3-ethoxy-4-methoxy-phenyl)-2-methanesulfonyl-ethyl]-7-nitro-2,3-dihydro-isoindol-1-one (3.0 g, 6.9 mmol) and Pd/C (10% 350 mg) in methanol/ethyl acetate (150 mL each) was shaken under hydrogen (50-60 psi) in a Parr for 20 hours. The suspension was filtered thru a pad of Celite, and washed with acetone (300 mL). The solvent was removed in vacuo to give a solid. The solid was slurried in methanol (10 mL) for 3 hours. The suspension was filtered and washed with methanol to give 7-amino-2-[(1S)-1-(3-ethoxy-4-methoxy-phenyl)-2-methanesulfonyl-ethyl]-2,3-dihydro-isoindol-1-one as a white solid (1.5 g, 55% yield): mp, 135-137° C.; 1H NMR (CDCl3) δ 1.44 (t, J=7 Hz, 3H, CH3), 2.93 (s, 3H, CH3), 3.66 (dd, J=5, 15 Hz, 1H, CHH), 3.85 (s, 3H, CH3), 4.06 (q, J=7 Hz, 2H, CH2), 4.13 (d, J=16 Hz, 1H, CHH), 4.22 (dd, J=10, 15 Hz, 1H, CHH), 4.35 (d, J=17 Hz, 1H, CHH), 5.19 (brs, 2H, NH2), 5.64 (dd, J=5, 10 Hz, 1H, NCH), 6.54 (d, J=8 Hz, 1H, Ar), 6.61 (d, J=7 Hz, 1H, Ar), 6.83 (d, J=8 Hz, 1H, Ar), 6.90-6.96 (m, 2H, Ar), 7.20 (t, J=8 Hz, 1H, Ar); 13C NMR (CDCl3) δ 14.59, 41.28, 48.01, 51.81, 55.87, 56.14, 64.48, 110.98, 111.38, 112.22, 113.41, 114.75, 119.23, 129.89, 133.08, 142.36, 146.02, 148.72, 149.45, 170.57; Anal Calcd for C20H24N2O5S: C, 59.39; H, 5.98; N, 6.93. Found: C, 59.04; H, 6.04; N, 6.74.

Workup

  1. filtrationThe suspension was filtered
  2. washwashed with acetone (300 mL)
  3. customThe solvent was removed in vacuo
  4. customto give a solid
  5. filtrationThe suspension was filtered
  6. washwashed with methanol

Sources & evidence

ORD record
ord-9a645f9443924fc088a995f7194d3e5d
Source dataset
uspto-grants-2014_05
Patent number
US08716252B2

Reaction notes

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