Benzofuran-2-carboxylic acid → HCID 58827279, compound

HRID 448464Notes

Reaction equation

HRID 448464 reaction equation
Cl.[NH2:2][CH2:3][C:4]1[CH:12]=[CH:11][CH:10]=[C:9]2[C:5]=1[C:6](=[O:22])[N:7]([CH:14]1[CH2:19][CH2:18][C:17](=[O:20])[NH:16][C:15]1=[O:21])[C:8]2=[O:13].N12CCCN=C1CCCCC2.[O:34]1[C:38]2[CH:39]=[CH:40][CH:41]=[CH:42][C:37]=2[CH:36]=[C:35]1[C:43](O)=[O:44].Cl.CN(C)CCCN=C=NCC>CC#N>[O:21]=[C:15]1[CH:14]([N:7]2[C:6](=[O:22])[C:5]3[C:9](=[CH:10][CH:11]=[CH:12][C:4]=3[CH2:3][NH:2][C:43]([C:35]3[O:34][C:38]4[CH:39]=[CH:40][CH:41]=[CH:42][C:37]=4[CH:36]=3)=[O:44])[C:8]2=[O:13])[CH2:19][CH2:18][C:17](=[O:20])[NH:16]1

Participants

6

Reactant 4

HCID 10331Benzofuran-2-carboxylic acidHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 219885254-(aminomethyl)-2-(2,6-dioxopiperidin-3-yl)-2,3-dihydro-1H-isoindole-1,3-dione hydrochloride

Product 1

HCID 58827279HCID 58827279, compoundYield 63%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a stirred suspension of 4-aminomethyl-2-(2,6-dioxo-piperidin-3-yl)-isoindole-1,3-dione hydrochloride (0.7 g, 2.2 mmol) in CH3CN (60 ml), was added 1,8-diazabicyclo[5.4.0]undec-7-ene (0.8 g, 5.4 mmol). After stirring for 10 minutes, 1-hydroxybenzenetriazole (0.35 g, 2.6 mmol) and 2-benzofuran carboxylic acid (0.39 g, 2.4 mmol) were added. To the reaction, was then added 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (0.62 g, 3.2 mmol), and the resulting mixture was stirred at room temperature overnight. The reaction mixture was then concentrated in vacuo, and the residue was dissolved in CH2Cl2 (50 mL). The CH2Cl2 solution was washed with water (2×30 mL) and brine (30 mL), and dried over MgSO4. Solvent was removed in vacuo, and the resulting oil was purified by ISCO silica gel flash chromatography (eluent: 30% EtOAc in CH2Cl2 for 10 min, then 40% EtOAc in CH2Cl2 for 10 min) to afford benzofuran-2-carboxylic acid [2-(2,6-dioxo-piperidin-3-yl)-1,3-dioxo-2,3-dihydro-1H-isoindol-4-ylmethyl]-amide as a white solid (0.59 g, 63%): mp, 292-295° C.; HPLC: Waters Symmetry C-18, 3.9×150 mm, 5 micro, 1 mL/min, 240 nm, 40/60 (CH3CN/H2O): tR=4.3 min. (98%); 1H NMR (DMSO-d6): δ 2.09-2.10 (m, 1H), 2.55-2.65 (m, 2H), 2.84-2.93 (m, 1H), 4.97 (d, J=6.0 Hz, 2H), 5.15-5.21 (dd, J=5, 12 Hz, 1H), 7.33-7.84 (m, 8H), 9.40 (t, J=6 Hz, 1H), 11.15 (s, 1H). 13C NMR (DMSO-d6) δ: 21.97, 30.92, 37.90, 48.87, 109.90, 111.79, 121.95, 122.81, 123.74, 126.96, 127.09, 127.15, 131.54, 133.02, 134.83, 138.71, 148.71, 154.27, 158.52, 166.94, 167.51, 169.82, 172.74. Anal Calcd for C23H17N3O6+0.2H2O: C, 63.51; H, 4.03; N, 9.66. Found: C, 63.45; H, 3.76; N, 9.52.

Workup

  1. customTo the reaction
  2. concentrationThe reaction mixture was then concentrated in vacuo
  3. dissolutionthe residue was dissolved in CH2Cl2 (50 mL)
  4. washThe CH2Cl2 solution was washed with water (2×30 mL) and brine (30 mL)
  5. dry with materialdried over MgSO4
  6. customSolvent was removed in vacuo
  7. customthe resulting oil was purified by ISCO silica gel flash chromatography (eluent
  8. wait30% EtOAc in CH2Cl2 for 10 min

Sources & evidence

ORD record
ord-55e965ce3989459bb2d0e2dd47630ae3
Source dataset
uspto-grants-2013_07
Patent number
US08481568B2

Reaction notes

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