Triethylamine → HCID 58827312, compound

HRID 448441Notes

Reaction equation

HRID 448441 reaction equation
[Br:1][C:2]1[N:7]=[C:6]([C:8]([OH:10])=O)[CH:5]=[CH:4][CH:3]=1.C1N=CN(C(N2C=NC=C2)=O)C=1.Cl.[NH2:24][CH2:25][C:26]1[CH:34]=[CH:33][CH:32]=[C:31]2[C:27]=1[C:28](=[O:44])[N:29]([CH:36]1[CH2:41][CH2:40][C:39](=[O:42])[NH:38][C:37]1=[O:43])[C:30]2=[O:35].C(N(CC)CC)C>CN(C=O)C>[O:43]=[C:37]1[CH:36]([N:29]2[C:28](=[O:44])[C:27]3[C:31](=[CH:32][CH:33]=[CH:34][C:26]=3[CH2:25][NH:24][C:8]([C:6]3[CH:5]=[CH:4][CH:3]=[C:2]([Br:1])[N:7]=3)=[O:10])[C:30]2=[O:35])[CH2:41][CH2:40][C:39](=[O:42])[NH:38]1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 682631,1'-CarbonyldiimidazoleHCID 5939196-Bromopyridine-2-carboxylic acidHCID 219885254-(aminomethyl)-2-(2,6-dioxopiperidin-3-yl)-2,3-dihydro-1H-isoindole-1,3-dione hydrochloride

Product 1

HCID 58827312HCID 58827312, compoundYield 53%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of 6-bromopicolinic acid (0.40 g, 2.0 mmol) and CDI (0.39 g, 2.4 mmol) in DMF (25 mL) was stirred at ambient temperature under nitrogen for 2 hours. 4-Aminomethyl-2-(2,6-dioxopiperidin-3-yl)isoindole-1,3-dione hydrochloride (0.65 g, 2.0 mmol) and triethylamine (0.61 g, 6.0 mmol) were added, and the mixture was allowed to stir for 16 hours. The solvent was evaporated under vacuum, and the residue was chromatographed using a methylene chloride-methanol gradient, eluting the product with 97:3 methylene chloride-methanol. This material was further purified by preparative HPLC, eluting with 1:1 acetonitrile-water, providing 0.50 g of the purified product in 53% yield: mp 181-183° C.; 1H NMR (DMSO-d6) δ 2.06-2.10 (m, 1H), 2.52-2.65 (m, 2H), 2.84-2.93 (m, 1H), 4.96 (d, J=6.3 Hz, 2H), 5.17 (dd, J=12.6 Hz, d=5.4 Hz, 1H), 7.67-7.72 (m, 1H), 7.80-7.82 (m, 2H), 7.90 (dd, J=7.8 Hz, J=1.0 Hz, 1H), 7.97 (t, J=7.6 Hz, 1H), 8.07 (dd, J=7.3 Hz, J=1.1 Hz, 1H), 9.39 (t, J=6.3 Hz, 1H), 11.15 (s, 1H); 13C NMR (DMSO-d6) δ 22.0, 30.9, 38.5, 48.9, 121.7, 121.9, 127.1, 131.2, 131.6, 133.0, 134.8, 138.9, 140.3, 141.0, 151.0, 163.1, 167.0, 167.6, 169.8, 172.8; Anal. calcd for C20H15BrN4O5.0.5H2O: C, 50.01; H, 3.35; N, 11.66. Found: C, 49.97; H, 3.21; N, 11.56.

Workup

  1. stirringto stir for 16 hours
  2. customThe solvent was evaporated under vacuum
  3. customthe residue was chromatographed
  4. washeluting the product with 97:3 methylene chloride-methanol
  5. customThis material was further purified by preparative HPLC
  6. washeluting with 1:1 acetonitrile-water

Sources & evidence

ORD record
ord-60c055e1758745d2937bd118d58ce82e
Source dataset
uspto-grants-2013_07
Patent number
US08481568B2

Reaction notes

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