1-Hydroxybenzotriazole → HCID 44194000, compound

HRID 1804737Notes

Reaction equation

HRID 1804737 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](O)=[O:20])=[CH:5]2.Cl.CN(C)CCCN=C=NCC.ON1C2C=CC=CC=2N=N1.[C:44]([N:47]1[C:51]2=[N:52][CH:53]=[C:54]([NH2:56])[CH:55]=[C:50]2[CH2:49][CH2:48]1)(=[O:46])[CH3:45]>CN(C=O)C>[C:44]([N:47]1[C:51]2=[N:52][CH:53]=[C:54]([NH:56][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:20])[CH:55]=[C:50]2[CH2:49][CH2:48]1)(=[O:46])[CH3:45]

Participants

6

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 574315135-fluoro-1-(3-fluorobenzyl)-1H-indole-2-carboxylic acidHCID 66845730HCID 66845730, compound

Product 1

HCID 44194000HCID 44194000, compoundYield 67%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
20 °C

Procedure

To a solution, stirred at 20° C., of 0.28 g (0.97 mmol) of 5-fluoro-1-(3-fluorobenzyl)-1H-indole-2-carboxylic acid prepared in step 1.1, 186 mg (0.97 mmol) of N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (EDAC) and 131 mg (0.97 mmol) of 1-hydroxybenzotriazole (HOBT) in 15 mL of DMF are added 206 mg (1.17 mmol) of 1-acetyl-5-amino-2,3-dihydro-1H-pyrrolo[2,3-b]pyridine, prepared in step 1.2. The reaction mixture is stirred for 14 hours at 20° C. and then concentrated under reduced pressure. The resulting product is taken up in 100 mL of water. The suspension is then extracted with three times 30 mL of ethyl acetate. The combined organic phases are washed twice with 20 mL of water, dried over sodium sulfate and then concentrated under reduced pressure. The product obtained is purified by chromatography on a column of silica, eluting with a mixture of dichloromethane and methanol. 290 mg of the expected product are thus isolated.

Workup

  1. customprepared in step 1.2
  2. concentrationconcentrated under reduced pressure
  3. extractionThe suspension is then extracted with three times 30 mL of ethyl acetate
  4. washThe combined organic phases are washed twice with 20 mL of water
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customThe product obtained
  8. customis purified by chromatography on a column of silica
  9. washeluting with a mixture of dichloromethane and methanol

Sources & evidence

ORD record
ord-c6d0f5bf05524669b259a8e1eedc40b4
Source dataset
uspto-grants-2013_01
Patent number
US08354425B2

Reaction notes

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