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

HRID 44195

Reaction equation

HRID 44195 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][N:25]=[CH:24][CH:23]=1.Cl>CC(C)=O.O>[N:25]1[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][CH:24]=1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 5234Sodium ChlorideHCID 91665PyroquilonHCID 6451240Aluminum(III) Chloride2×HCID 12262826Isonicotinoyl chloride hydrochloride

Product 1

HCID 444798808-(Pyridine-4-carbonyl)-1,2,5,6-tetrahydro-pyrrolo[3,2,1-ij]quinolin-4-oneYield 27%

Reagents, catalysts & solvents 2

HCID 180AcetoneSolventHCID 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 isonicotinoylchloride 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 acetone gave the acylation product (751 mg, 2.70 mmol, 27%) as a yellow solid, mp (acetone) 184° C. 1H-NMR (500 MHz, CDCl3): δ=2.70 (t, 3J=7.7 Hz, 2H), 2.99 (t, 3J=7.8 Hz, 2H), 3.21 (t, 3J=8.2 Hz, 2H), 4.12 (t, 3J=8.2 Hz, 2H), 7.49 (m, 3H), 7.55 (s, 1H), 8.76 (d, 3J=5.1 Hz, 2H), 13C-NMR (125 MHz, CDCl3): δ=24.1, 27.2, 31.3, 45.7, 119.9, 122.6, 126.1, 129.0, 129.4, 131.4, 145.3, 146.3, 150.2, 167.8, 193.9. MS m/z 279.07 (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 acetone

Sources & evidence

ORD record
ord-8070d91b038743d8858a17e37cf1cc7d
Source dataset
uspto-grants-2013_09
Patent number
US08541404B2

Linked notes

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