(S)-3-amino-3-methylpiperidine-2,6-dione hydrobromide → HCID 58827262, compound

HRID 448408Notes

Reaction equation

HRID 448408 reaction equation
[CH2:1]1[C:9]2[C:4](=[CH:5][C:6]([NH:10][C:11]3[CH:19]=[CH:18][CH:17]=[C:13]([C:14](O)=[O:15])[C:12]=3[C:20]([OH:22])=O)=[CH:7][CH:8]=2)[CH2:3][CH2:2]1.Br.[NH2:24][C@@:25]1([CH3:33])[CH2:30][CH2:29][C:28](=[O:31])[NH:27][C:26]1=[O:32]>N1C=CC=CC=1>[CH2:1]1[C:9]2[C:4](=[CH:5][C:6]([NH:10][C:11]3[CH:19]=[CH:18][CH:17]=[C:13]4[C:12]=3[C:20](=[O:22])[N:24]([C@@:25]3([CH3:33])[CH2:30][CH2:29][C:28](=[O:31])[NH:27][C:26]3=[O:32])[C:14]4=[O:15])=[CH:7][CH:8]=2)[CH2:3][CH2:2]1

Participants

4

Reactant 2

HCID 66643102(S)-3-amino-3-methylpiperidine-2,6-dione hydrobromideHCID 672296193-(Indan-5-ylamino)-phthalic acid

Product 1

HCID 58827262HCID 58827262, compoundYield 45%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

A mixture of 3-(indan-5-ylamino)-phthalic acid (0.62 g, 3.1 mmol) and (3S)-3-amino-3-methyl-piperidine-2,6-dione hydrobromide (0.50 g, 2.1 mmol) in pyridine (10 mL) was heated to reflux for 17 hours. The mixture was cooled and evaporated under vacuum. The residue was dissolved in ethyl acetate (100 mL), washed with dilute aqueous HCl (2×100 mL) and water (2×100 mL), and evaporated. The residue was purified by ISCO silica gel flash chromatography using a hexanes-ethyl acetate gradient, eluting 0.37 g of the product, an orange solid, at 70:30 hexanes-ethyl acetate, in 45% yield: mp 200-202° C.; HPLC, Waters Symmetry C-18, 3.9×150 mm, 5 μm, 1 mL/min, 240 nm, 65/35 (CH3CN/0.1% H3PO4): tR=5.40 (99.54%); 1H NMR (DMSO-d6) δ 1.91 (s, 3H), 2.00-2.08 (m, 3H), 2.54-2.75 (m, 3H), 2.82-2.88 (m, 4H), 7.04-7.31 (m, 5H), 7.55 (t, J=7.8 Hz, 1H), 8.30 (s, 1H), 11.00 (s, 1H); 13C NMR (DMSO-d6) δ 21.0, 25.2, 28.6, 29.2, 31.8, 32.4, 58.5, 110.9, 112.4, 118.7, 120.7, 124.9, 132.2, 136.0, 137.2, 139.9, 143.4, 145.1, 167.8, 169.4, 172.2, 172.3; Anal. calcd for C23H21N3O4: C, 68.47; H, 5.25; N, 10.42. Found: C, 68.25; H, 5.12; N, 10.30.

Workup

  1. temperaturewas heated
  2. temperatureto reflux for 17 hours
  3. temperatureThe mixture was cooled
  4. customevaporated under vacuum
  5. dissolutionThe residue was dissolved in ethyl acetate (100 mL)
  6. washwashed with dilute aqueous HCl (2×100 mL) and water (2×100 mL)
  7. customevaporated
  8. customThe residue was purified by ISCO silica gel flash chromatography
  9. washeluting 0.37 g of the product

Sources & evidence

ORD record
ord-4ba55c11e5ad4befafc3edd65aecc1ba
Source dataset
uspto-grants-2013_07
Patent number
US08481568B2

Reaction notes

Loading…