Pyridinium chloride → 4-[3-chloro-4-(1-methyl-1H-imidazol-2-ylsulfanyl)phenylamino]-7-methoxy-8-(2-morpholin-4-yl-ethoxy)benzo[g]quinoline-3-carbonitrile

HRID 902421Notes

Reaction equation

HRID 902421 reaction equation
Cl[C:2]1[C:11]2[C:6](=[CH:7][C:8]3[CH:15]=[C:14]([O:16][CH2:17][CH2:18][N:19]4[CH2:24][CH2:23][O:22][CH2:21][CH2:20]4)[C:13]([O:25][CH3:26])=[CH:12][C:9]=3[CH:10]=2)[N:5]=[CH:4][C:3]=1[C:27]#[N:28].[Cl:29][C:30]1[CH:31]=[C:32]([NH2:43])[CH:33]=[CH:34][C:35]=1[S:36][C:37]1[N:38]([CH3:42])[CH:39]=[CH:40][N:41]=1.Cl.N1C=CC=CC=1>C(OCCO)C.CCOCC>[Cl:29][C:30]1[CH:31]=[C:32]([NH:43][C:2]2[C:11]3[C:6](=[CH:7][C:8]4[CH:15]=[C:14]([O:16][CH2:17][CH2:18][N:19]5[CH2:20][CH2:21][O:22][CH2:23][CH2:24]5)[C:13]([O:25][CH3:26])=[CH:12][C:9]=4[CH:10]=3)[N:5]=[CH:4][C:3]=2[C:27]#[N:28])[CH:33]=[CH:34][C:35]=1[S:36][C:37]1[N:38]([CH3:42])[CH:39]=[CH:40][N:41]=1

Participants

6

Reactant 3

HCID 10176127Pyridinium chlorideHCID 114590883-chloro-4-(1-methyl-1H-imidazol-2-ylsulfanyl)phenylamineHCID 120627424-Chloro-7-methoxy-8-(2-morpholin-4-yl ethoxy)benzo[g]quinoline-3-carbonitrile

Product 1

HCID 101454084-[3-chloro-4-(1-methyl-1H-imidazol-2-ylsulfanyl)phenylamino]-7-methoxy-8-(2-morpholin-4-yl-ethoxy)benzo[g]quinoline-3-carbonitrileYield 59.1%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 8076Glycol monoethyl etherSolvent

Conditions

Temperature
120 °C

Procedure

A mixture of 1.98 g (4.98 mmol) of 4-chloro-7-methoxy-8-(2-morpholin-4-yl-ethoxy)benzo[g]quinoline-3-carbonitrile, 1.31 g (5.47 mmol) of 3-chloro-4(1-methyl-1H-imidazol-2-ylsulfanyl)phenylamine and 0.6 g (5.2 mmol) of pyridine hydrochloride in 2-ethoxyethanol is heated at 120° C. for 1.25 hours, then cooled. The crude mixture is poured into a solution of saturated sodium bicarbonate/ice and stirred for 45 minutes. The resulting solid is collected by filtration, then washed with water, ether and ethyl acetate successively. After drying in vacuo, the solid is purified by silica gel chromatography, using a 94:6 to 9:1 gradient of methylene chloride/methanol to provide a yellow solid. This solid is suspended in ether, filtered, and further washed with ether. After drying in vacuo, 1.77 g of 4-[3-chloro-4-(1-methyl-1H-imidazol-2-ylsulfanyl)phenylamino]-7-methoxy-8-(2-morpholin-4-yl-ethoxy)benzo[g]quinoline-3-carbonitrile is obtained as a yellow solid, mp.>300° C.

Workup

  1. temperaturecooled
  2. filtrationThe resulting solid is collected by filtration
  3. washwashed with water, ether and ethyl acetate successively
  4. customAfter drying in vacuo
  5. customthe solid is purified by silica gel chromatography
  6. customto provide a yellow solid
  7. filtrationfiltered
  8. washfurther washed with ether
  9. customAfter drying in vacuo

Sources & evidence

ORD record
ord-d20b11eea8854fcb85f3181129bd715f
Source dataset
uspto-grants-2008_04
Patent number
US07365197B2

Reaction notes

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