Dimethylamine → 4-[(7-chloro-4-methyl-1H-indol-5-yl)amino]-5-{4-[2-(dimethylamino)ethoxy]phenyl}nicotinonitrile

HRID 506209Notes

Reaction equation

HRID 506209 reaction equation
Cl[CH2:2][CH2:3][O:4][C:5]1[CH:10]=[CH:9][C:8]([C:11]2[CH:12]=[N:13][CH:14]=[C:15]([C:18]=2[NH:19][C:20]2[C:21]([CH3:30])=[C:22]3[C:26](=[C:27]([Cl:29])[CH:28]=2)[NH:25][CH:24]=[CH:23]3)[C:16]#[N:17])=[CH:7][CH:6]=1.[CH3:31][NH:32][CH3:33]>C1COCC1.COCCOC>[Cl:29][C:27]1[CH:28]=[C:20]([NH:19][C:18]2[C:15]([C:16]#[N:17])=[CH:14][N:13]=[CH:12][C:11]=2[C:8]2[CH:9]=[CH:10][C:5]([O:4][CH2:3][CH2:2][N:32]([CH3:33])[CH3:31])=[CH:6][CH:7]=2)[C:21]([CH3:30])=[C:22]2[C:26]=1[NH:25][CH:24]=[CH:23]2

Participants

5

Reactant 2

HCID 674DimethylamineHCID 684656455-[4-(2-chloroethoxy)phenyl]-4-[(7-chloro-4-methyl-1H-indol-5-yl)amino]nicotinonitrile

Product 1

HCID 684620114-[(7-chloro-4-methyl-1H-indol-5-yl)amino]-5-{4-[2-(dimethylamino)ethoxy]phenyl}nicotinonitrileYield 74%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 80711,2-DimethoxyethaneSolvent

Procedure

A solution of 5-[4-(2-chloroethoxy)phenyl]-4-[(7-chloro-4-methyl-1H-indol-5-yl)amino]nicotinonitrile (144 mg, 0.3 mmol) and dimethyl amine (1.7 mL of a 2.0 M solution in THF, 3.4 mmol) in DME (3 mL) in a sealed tube was stirred at 110° C. for 48 h and cooled to room temperature. After the resulting solution was concentrated, 1 N aqueous HCl was added and the aqueous phase was extracted with ethyl acetate and the aqueous solution was adjusted to pH of 10 by adding sodium carbonate and extracted with ethyl acetate. The combined organic phases were washed with water and brine, dried over magnesium sulfate, and concentrated to give 4-[(7-chloro-4-methyl-1H-indol-5-yl)amino]-5-{4-[2-(dimethylamino)ethoxy]phenyl}nicotinonitrile as a yellow solid (109 mg, 74%). HPLC retention time: 5.1 min.(g); MS: 446.3 (M+H); and HRMS: 446.1743.

Workup

  1. concentrationAfter the resulting solution was concentrated
  2. addition1 N aqueous HCl was added
  3. extractionthe aqueous phase was extracted with ethyl acetate
  4. additionby adding sodium carbonate
  5. extractionextracted with ethyl acetate
  6. washThe combined organic phases were washed with water and brine
  7. dry with materialdried over magnesium sulfate
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-9b610627bc344ece9632ea1988a7c974
Source dataset
uspto-grants-2010_08
Patent number
US07781591B2

Reaction notes

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