Triethylamine → N-(2,3-Dimethyl-3H-imidazo[4,5-b]pyrid-6-yl)-5-fluoro-1-(3-fluorobenzyl)-1H-indole-2-carboxamide

HRID 2069520Notes

Reaction equation

HRID 2069520 reaction equation
[F:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([CH2:11][C:12]1[CH:17]=[CH:16][CH:15]=[C:14]([F:18])[CH:13]=1)[C:6]([C:19]([OH:21])=O)=[CH:5]2.Cl.CN(C)CCCN=C=NCC.ON1C2C=CC=CC=2N=N1.C(N(CC)CC)C.Cl.[NH2:52][C:53]1[CH:54]=[C:55]2[N:61]=[C:60]([CH3:62])[N:59]([CH3:63])[C:56]2=[N:57][CH:58]=1>CN(C=O)C>[CH3:62][C:60]1[N:59]([CH3:63])[C:56]2=[N:57][CH:58]=[C:53]([NH:52][C:19]([C:6]3[N:7]([CH2:11][C:12]4[CH:17]=[CH:16][CH:15]=[C:14]([F:18])[CH:13]=4)[C:8]4[C:4]([CH:5]=3)=[CH:3][C:2]([F:1])=[CH:10][CH:9]=4)=[O:21])[CH:54]=[C:55]2[N:61]=1

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 574315135-fluoro-1-(3-fluorobenzyl)-1H-indole-2-carboxylic acidHCID 66890088HCID 66890088, compound

Product 1

HCID 44181663N-(2,3-Dimethyl-3H-imidazo[4,5-b]pyrid-6-yl)-5-fluoro-1-(3-fluorobenzyl)-1H-indole-2-carboxamideYield 40%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
20 °C

Procedure

To a solution, stirred at 20° C., of 0.25 g (0.87 mmol) of 5-fluoro-1-(3-fluorobenzyl)-1H-indole-2-carboxylic acid prepared in step 1.1, 183 mg (0.96 mmol) of N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (EDAC) and 129 mg (0.96 mmol) of 1-hydroxybenzotriazole (HOBT) in 8 mL of DMF are added 130 microliters (0.96 mol) of triethylamine and then 224 mg (1.13 mmol) of 6-amino-2,3-dimethyl-3H-imidazo[4,5-b]pyridine hydrochloride (Ukrainskii Khimicheskii Zhurnal 1981, 47, 867). The reaction mixture is stirred for 8 hours at 20° C. and then concentrated under reduced pressure. The resulting product is taken up in 100 mL of water, and a precipitate is collected by filtration and is purified by chromatography on a column of silica, eluting with a mixture of dichloromethane and methanol. The fractions containing the product are combined and evaporated to a quarter of their volume. 50 mL of n-heptane are added to the solution, and a solid is collected by filtration and dried under reduced pressure. 150 mg of the expected product are thus isolated.

Workup

  1. concentrationconcentrated under reduced pressure
  2. filtrationa precipitate is collected by filtration
  3. customis purified by chromatography on a column of silica
  4. washeluting with a mixture of dichloromethane and methanol
  5. additionThe fractions containing the product
  6. customevaporated to a quarter of their volume
  7. addition50 mL of n-heptane are added to the solution
  8. filtrationa solid is collected by filtration
  9. customdried under reduced pressure

Sources & evidence

ORD record
ord-2d1cd1ab6d4a4a3cb28a343c02e07c80
Source dataset
uspto-grants-2012_10
Patent number
US08299114B2

Reaction notes

Loading…