Triethylamine → 2,3-Dihydrothieno[3,2-b]quinolin-9-amine

HRID 1590314Notes

Reaction equation

HRID 1590314 reaction equation
[S:1]1[CH2:5][CH2:4][C:3](=O)[CH2:2]1.C(N(CC)CC)C.[C:14](#[N:22])[C:15]1[C:16](=[CH:18][CH:19]=[CH:20][CH:21]=1)[NH2:17]>C(Cl)Cl.[Ti](Cl)(Cl)(Cl)Cl>[S:1]1[C:2]2[C:3](=[N:17][C:16]3[CH:18]=[CH:19][CH:20]=[CH:21][C:15]=3[C:14]=2[NH2:22])[CH2:4][CH2:5]1

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 61252Dihydro-3(2H)-thiophenone2×HCID 729132-Aminobenzonitrile

Product 1

HCID 143728282,3-Dihydrothieno[3,2-b]quinolin-9-amineYield 64.3%

Reagents, catalysts & solvents 2

HCID 24193Titanium TetrachlorideCatalyst2×HCID 6344DichloromethaneSolvent3×

Procedure

To a stirred solution of tetrahydrothiophen-3-one (1.1 g, 11 mmole) in methylene chloride (10 ml) at -78° C., a 1M solution of titanium (IV) chloride in methylene chloride (11 ml) was added. A mixture of triethylamine (2.2 g, 22 mmole) and anthranilonitrile (1.2 gms, 10.0 mmole) in methylene chloride (30 ml) was then added to the reaction mixture over a period of 5 minutes. The reaction mixture was then slowly warmed to room temperature and stirred for 2 hours. Tetrahydrothiophen-3-one (1 ml) and titanium(IV) chloride (1.0 ml) was then added to the reaction mixture and the mixture was stirred at 25° C. for 16 hours. Thereafter, the reaction mixture was quenched with 12% aqueous NaOH (100 ml) and the reaction mixture was then stirred vigorously with additional methylene chloride (300 ml). The reaction mixture was then filtered through diatomaceous earth (Celite (trademark)) and the organic phase was separated. The organic solvents were removed under vacuum to afford a residue which was loaded on a flash chromatography column. Elution with 5% methanol in methylene chloride containing 1% triethylamine, afforded the title compound (1.3 gms, 64%) which was crystallized from chloroform (560 mg, 32%, m.p. 208°-210° C.). 1H-NMR (CDCl3, 300 MHz, δ): 4H, m, 3.4-3.56 ppm; 2H, bs, 4.51 ppm; 1H, dt, 7.37 ppm (J=7.0, 1.0 Hz); 1H, dt, 7.52 ppm (J=7.0, 1.10 ppm); 1H, dd, 7.61 ppm (J=7.0, 1.0 ppm); 1H, dd, 7.61 ppm (J=7.0, 1.0 ppm), 1H, dd, 7.86 ppm (J=7.0, 1.0 ppm). HRMS: Calculated--202.0575; Found--202.0545.

Workup

  1. additionwas then added to the reaction mixture over a period of 5 minutes
  2. stirringthe mixture was stirred at 25° C. for 16 hours
  3. customThereafter, the reaction mixture was quenched with 12% aqueous NaOH (100 ml)
  4. stirringthe reaction mixture was then stirred vigorously with additional methylene chloride (300 ml)
  5. filtrationThe reaction mixture was then filtered through diatomaceous earth (Celite (trademark))
  6. customthe organic phase was separated
  7. customThe organic solvents were removed under vacuum
  8. customto afford a residue which
  9. washElution with 5% methanol in methylene chloride containing 1% triethylamine

Sources & evidence

ORD record
ord-cfbe04a1779b438f84c5ecb084c1292b
Source dataset
uspto-grants-1993_04
Patent number
US05202440

Reaction notes

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