Acetonitrile → 5-{[2-(2,6-Dioxo-piperidin-3-YL)-1,3-dioxo-2,3-dihydro-1H-isoindol-5-ylmethyl]-carbamoyl}-pentanoic acid

HRID 331541Notes

Reaction equation

HRID 331541 reaction equation
C([O:5][C:6](=[O:34])[CH2:7][CH2:8][CH2:9][CH2:10][C:11](=[O:33])[NH:12][CH2:13][C:14]1[CH:15]=[C:16]2[C:20](=[CH:21][CH:22]=1)[C:19](=[O:23])[N:18]([CH:24]1[CH2:29][CH2:28][C:27](=[O:30])[NH:26][C:25]1=[O:31])[C:17]2=[O:32])(C)(C)C.CC#N>C(O)=O>[O:31]=[C:25]1[CH:24]([N:18]2[C:17](=[O:32])[C:16]3[C:20](=[CH:21][CH:22]=[C:14]([CH2:13][NH:12][C:11]([CH2:10][CH2:9][CH2:8][CH2:7][C:6]([OH:34])=[O:5])=[O:33])[CH:15]=3)[C:19]2=[O:23])[CH2:29][CH2:28][C:27](=[O:30])[NH:26]1

Participants

4

Reactant 2

HCID 6342AcetonitrileHCID 247889725-{[2-(2,6-dioxo-piperidin-3-yl)-1,3-dioxo-2,3-dihydro-1H-isoindol-5-ylmethyl]-carbamoyl}-pentanoic acid tert-butyl ester

Product 1

HCID 247889735-{[2-(2,6-Dioxo-piperidin-3-YL)-1,3-dioxo-2,3-dihydro-1H-isoindol-5-ylmethyl]-carbamoyl}-pentanoic acidYield 88%

Reagents, catalysts & solvents 1

HCID 284Formic AcidSolvent

Procedure

A solution of 5-{[2-(2,6-dioxo-piperidin-3-yl)-1,3-dioxo-2,3-dihydro-1H-isoindol-5-ylmethyl]-carbamoyl}-pentanoic acid tert-butyl ester (0.85 g, 1.8 mmol) in formic acid (25 mL) was stirred at room temperature for 90 minutes. The mixture was evaporated under vacuum, and the residue was triturated in ether/ethyl acetate and filtered, providing 0.66 g, in 88% yield; mp 144-146° C.; HPLC, Waters Symmetry C-18, 3.9×150 mm, 5 μm, 1 mL/min, 240 nm, 20/80 CH3CN/0.1% H3PO4, 4.15 (95.81%); 1H NMR (DMSO-d6) δ 1.44-1.59 (m, 4H), 2.02-2.09 (m, 1H), 2.16-2.24 (m, 4H), 2.46-2.63 (m, 2H), 2.83-2.95 (m, 1H), 4.43 (d, J=6.0 Hz, 2H), 5.14 (dd, J=12.9 Hz, J=5.4 Hz, 1H), 7.72-7.77 (m, 2H), 7.87 (d, J=7.8 Hz, 1H), 8.51 (t, J=6.0 Hz, 1H), 11.12 (s, 1H), 12.00 (s, 1H); 13C NMR (DMSO-d6) δ 22.0, 24.1, 24.7, 30.9, 33.3, 34.9, 41.9, 48.9, 121.9, 123.5, 129.7, 131.6, 133.3, 147.8, 167.0, 167.1, 169.8, 172.2, 172.7, 174.3; Anal. Calcd for C20H21N3O7+0.2H2O: C, 57.33; H, 5.13; N, 10.03. Found: C, 57.33; H, 4.89; N, 9.81.

Workup

  1. customThe mixture was evaporated under vacuum
  2. customthe residue was triturated in ether/ethyl acetate
  3. filtrationfiltered
  4. customproviding 0.66 g

Sources & evidence

ORD record
ord-813c66d726104268b088c8dfad8324c5
Source dataset
uspto-grants-2014_11
Patent number
US08877780B2

Reaction notes

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