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

HRID 63402Notes

Reaction equation

HRID 63402 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-6927dad048dc406ebedd91fb52595d96
Source dataset
uspto-grants-2016_09
Patent number
US09447070B2

Reaction notes

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