Hydrochloric Acid → 8-(Pyridine-3-carbonyl)-1,2,5,6-tetrahydro-pyrrolo[3,2,1-ij]quinolin-4-one

HRID 44196

Reaction equation

HRID 44196 reaction equation
[Al+3].[Cl-].[Cl-].[Cl-].[Na+].[Cl-].[CH2:7]1[C:17]2=[C:18]3[C:13](=[CH:14][CH:15]=[CH:16]2)[CH2:12][CH2:11][C:10](=[O:19])[N:9]3[CH2:8]1.Cl.[C:21](Cl)(=[O:28])[C:22]1[CH:27]=[CH:26][CH:25]=[N:24][CH:23]=1.Cl>C(O)C.O>[N:24]1[CH:25]=[CH:26][CH:27]=[C:22]([C:21]([C:15]2[CH:14]=[C:13]3[C:18]4=[C:17]([CH2:7][CH2:8][N:9]4[C:10](=[O:19])[CH2:11][CH2:12]3)[CH:16]=2)=[O:28])[CH:23]=1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 5234Sodium ChlorideHCID 884383-Pyridinecarbonyl chloride, hydrochloride (1:1)HCID 91665PyroquilonHCID 6451240Aluminum(III) Chloride2×

Product 1

HCID 444798818-(Pyridine-3-carbonyl)-1,2,5,6-tetrahydro-pyrrolo[3,2,1-ij]quinolin-4-oneYield 22.4%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 962WaterSolvent

Procedure

To a molten mixture of AlCl3 (8.0 g, 60.0 mmol) and NaCl (2.34 g, 40.0 mmol) at 150° C. was added 1,2,5,6-tetrahydro-pyrrolo[3,2,1-ij]quinolin-4-one (1.79 g, 10.0 mmol) and thereafter nicotinoylchloride hydrochloride salt (1.96 g, 11.0 mmol) portionwise. After stirring for 15 min and cooling to room temperature, excess aluminum chloride was decomposed by the addition of a chilled mixture of 10 ml concentrated hydrochloric acid and 200 ml water. Neutralization with NaHCO3 solution and subsequent extraction with ethyl acetate (3×100 ml), followed by drying over MgSO4 and removal of the solvent gave the crude product. Purification by crystallization from ethanol gave the acylation product (624 mg, 2.24 mmol, 22%) as a yellow solid, mp (ethanol) 147° C. 1H-NMR (500 MHz, CDCl3): δ=2.72 (t, 3J=7.9 Hz, 2H), 3.02 (t, 3J=7.9 Hz, 2H), 3.23 (t, 3J=8.6 Hz, 2H), 4.14 (t, 3J=8.6 Hz, 2H), 7.44 (ddd, 3J=7.9 Hz, 3J=4.7 Hz, 5J=1.0 Hz, 1H), 7.53 (s, 1H), 7.58 (s, 1H), 8.06 (m, 1H), 8.78 (dd, 3J=5.0 Hz, 4J=1.9 Hz, 1H), 8.92 (dd, 4J=1.9 Hz, 5J=0.8 Hz, 1H). 13C-NMR (125 MHz, CDCl3): δ=24.2, 27.3, 31.4, 45.8, 199.9, 123.4, 126.1, 128.9, 129.4, 132.3, 134.0, 137.0, 146.1, 150.4, 152.4, 167.8, 193.6. MS m/z 278.79 (MH+).

Workup

  1. extractionNeutralization with NaHCO3 solution and subsequent extraction with ethyl acetate (3×100 ml)
  2. dry with materialby drying over MgSO4 and removal of the solvent
  3. customgave the crude product
  4. customPurification
  5. customby crystallization from ethanol

Sources & evidence

ORD record
ord-65f42044164a4c2e93c4763e6f251c5c
Source dataset
uspto-grants-2013_09
Patent number
US08541404B2

Linked notes

Loading…