Acetonitrile → 7-Methoxy-8-(2-morpholin-4-yl-ethoxy)4-oxo-1,4-dihydrobenzo[g]quinoline-3-carbonitrile

HRID 2213818Notes

Reaction equation

HRID 2213818 reaction equation
C([Li])CCC.[C:6](#[N:8])[CH3:7].C(O[C:14]([C:16]1[C:25]([N:26]=[CH:27]N(C)C)=[CH:24][C:23]2[C:18](=[CH:19][C:20]([O:40][CH3:41])=[C:21]([O:31][CH2:32][CH2:33][N:34]3[CH2:39][CH2:38][O:37][CH2:36][CH2:35]3)[CH:22]=2)[CH:17]=1)=[O:15])(C)(C)C>O1CCCC1>[CH3:41][O:40][C:20]1[C:21]([O:31][CH2:32][CH2:33][N:34]2[CH2:35][CH2:36][O:37][CH2:38][CH2:39]2)=[CH:22][C:23]2[CH:24]=[C:25]3[C:16]([C:14](=[O:15])[C:7]([C:6]#[N:8])=[CH:27][NH:26]3)=[CH:17][C:18]=2[CH:19]=1

Participants

5

Reactant 3

HCID 6342AcetonitrileHCID 12062740HCID 12062740, compoundHCID 178418339Butyllithium

Product 1

HCID 120627417-Methoxy-8-(2-morpholin-4-yl-ethoxy)4-oxo-1,4-dihydrobenzo[g]quinoline-3-carbonitrile

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

To 15 mL of tetrahydrofuran at −78° C. is added 2.6 mL of n-butyllithium (1.6M in hexane) and the reaction mixture is stirred for 5 minutes. To this is added 0.36 mL (6.8 mmol) of acetonitrile dropwise, followed by stirring for 15 minutes. Finally, a solution of 3-(dimethylamino-methyleneamino)-7-methoxy-6-(2-morpholin-4-yl-ethoxy)naphthalene-2-carboxylic acid tert-butyl ester in 5 mL of tetrahydrofuran is added dropwise over a period of 15 minutes. The resulting mixture is stirred at −78° C. for 1 hour, then at room temperature for 1 hour. After cooling again to −78° C., the reaction is quenched with 0.5 mL of glacial acetic acid, the dry ice bath is removed and the resulting thick slurry is stirred for 1 hour. The solid is collected by filtration, washed with ethyl acetate and dried. Purification is carried out by silica gel chromatography, utilizing a gradient of 95:5 to 89:11 of methylene chloride/methanol to give 0.38 g of 7-methoxy-8-(2-morpholin-4-yl-ethoxy)-4-oxo-1,4-dihydrobenzo[g]quinoline-3-carbonitrile as a yellow solid, mp 275° C. (dec).

Workup

  1. stirringby stirring for 15 minutes
  2. stirringThe resulting mixture is stirred at −78° C. for 1 hour
  3. waitat room temperature for 1 hour
  4. customthe reaction is quenched with 0.5 mL of glacial acetic acid
  5. customthe dry ice bath is removed
  6. stirringthe resulting thick slurry is stirred for 1 hour
  7. filtrationThe solid is collected by filtration
  8. washwashed with ethyl acetate
  9. customdried
  10. customPurification

Sources & evidence

ORD record
ord-84cdfd889c704cf391cf2d309b61209e
Source dataset
uspto-grants-2006_09
Patent number
US07105531B2

Reaction notes

Loading…