Diisopropylethylamine → Benzo[b]thiophene-2-carboxylic acid[2-(2,6-dioxo-piperidin-3-yl)-1,3-dioxo-2,3-dihydro-1h-isoindol-5-ylmethyl]-amide

HRID 331600Notes

Reaction equation

HRID 331600 reaction equation
Cl.[NH2:2][CH2:3][C:4]1[CH:5]=[C:6]2[C:10](=[CH:11][CH:12]=1)[C:9](=[O:13])[N:8]([CH:14]1[CH2:19][CH2:18][C:17](=[O:20])[NH:16][C:15]1=[O:21])[C:7]2=[O:22].[S:23]1[C:27]([C:28](Cl)=[O:29])=[CH:26][C:25]2[CH:31]=[CH:32][CH:33]=[CH:34][C:24]1=2.CCN(C(C)C)C(C)C>CC#N>[O:21]=[C:15]1[CH:14]([N:8]2[C:7](=[O:22])[C:6]3[C:10](=[CH:11][CH:12]=[C:4]([CH2:3][NH:2][C:28]([C:27]4[S:23][C:24]5[CH:34]=[CH:33][CH:32]=[CH:31][C:25]=5[CH:26]=4)=[O:29])[CH:5]=3)[C:9]2=[O:13])[CH2:19][CH2:18][C:17](=[O:20])[NH:16]1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 142384Benzo[b]thiophene-2-carbonyl ChlorideHCID 670197065-(Aminomethyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione hydrochloride

Product 1

HCID 57730498Benzo[b]thiophene-2-carboxylic acid[2-(2,6-dioxo-piperidin-3-yl)-1,3-dioxo-2,3-dihydro-1h-isoindol-5-ylmethyl]-amideYield 56%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a stirred mixture of 5-aminomethyl-2-(2,6-dioxo-piperidin-3-yl)-isoindole-1,3-dione hydrochloride (0.97 g, 3.00 mmol) and benzo[b]thiophene-2-carbonyl chloride (0.59 g, 3.00 mmol) in MeCN (20 mL), was added DIPEA (1.05 mL, 6.00 mmol) at room temperature under nitrogen. After 1 h, the solvent was removed in vacuo and the residue was dissolved in EtOAc (100 mL). The organic layer was washed with dil. aq. HCl (2×150 mL), water (100 mL), dried (MgSO4) and then concentrated. The product was dried in vacuo to give benzo[b]thiophene-2-carboxylic acid[2-(2,6-dioxo-piperidin-3-yl)-1,3-dioxo-2,3-dihydro-1H-isoindol-5-ylmethyl]-amide as a white solid (0.75 g, 56% yield): HPLC: Waters Symmetry C18, 5 μm, 3.9×150 mm, 1 mL/min, 240 nm, 40/60 CH3CN/0.1% H3PO4, 7.03 min (96.23%); mp: 318-320° C.; 1H NMR (DMSO-d6) δ 1.96-2.17 (m, 1H, CHH), 2.54-2.68 (m, 2H, CHH, CHH), 2.78-3.00 (m, 1H, CHH), 4.68 (d, J=5.9 Hz, 2H, CH2), 5.15 (dd, J=5.4, 12.7 Hz, 1H, CH), 7.39-7.55 (m, 2H, Ar), 7.79-8.10 (m, 5H, Ar), 8.16 (s, 1H, Ar), 9.50 (t, J=5.9 Hz, 1H, NH), 11.13 (s, 1H, NH); 13C NMR (DMSO-d6) δ 21.99, 30.93, 42.64, 49.01, 122.07, 122.83, 123.63, 124.97, 125.25, 126.32, 129.93, 131.66, 133.54, 139.10, 139.27, 140.25, 147.13, 161.80, 166.96, 167.10, 169.82, 172.73; LCMS: MH=448; Anal Calcd for C23H17N3O5S: C, 61.74; H, 3.83; N, 9.39. Found: C, 61.59; H, 3.53; N, 9.29.

Workup

  1. customthe solvent was removed in vacuo
  2. dissolutionthe residue was dissolved in EtOAc (100 mL)
  3. washThe organic layer was washed with dil. aq. HCl (2×150 mL), water (100 mL)
  4. dry with materialdried (MgSO4)
  5. concentrationconcentrated
  6. customThe product was dried in vacuo

Sources & evidence

ORD record
ord-ad30ffc904494e5fa480d99607ba8497
Source dataset
uspto-grants-2014_11
Patent number
US08877780B2

Reaction notes

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