1-Hydroxybenzotriazole → HCID 66850586, compound

HRID 1948797Notes

Reaction equation

HRID 1948797 reaction equation
Cl.CN(C)CCCN=C=NCC.ON1C2C=CC=CC=2N=N1.[Br:23][C:24]1[CH:25]=[C:26]2[C:30](=[CH:31][CH:32]=1)[N:29]([CH2:33][C:34]1[CH:39]=[CH:38][CH:37]=[C:36]([F:40])[CH:35]=1)[C:28]([C:41](O)=[O:42])=[CH:27]2.[NH2:44][C:45]1[CH:46]=[N:47][C:48]([N:51]2[CH2:54][CH2:53][CH2:52]2)=[CH:49][CH:50]=1>CN(C=O)C.C(OCC)(=O)C.O>[N:51]1([C:48]2[N:47]=[CH:46][C:45]([NH:44][C:41]([C:28]3[N:29]([CH2:33][C:34]4[CH:39]=[CH:38][CH:37]=[C:36]([F:40])[CH:35]=4)[C:30]4[C:26]([CH:27]=3)=[CH:25][C:24]([Br:23])=[CH:32][CH:31]=4)=[O:42])=[CH:50][CH:49]=2)[CH2:54][CH2:53][CH2:52]1

Participants

8

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 552816836-(1-Azetidinyl)-3-pyridinamineHCID 668503725-bromo-1-[(3-fluorophenyl)methyl]-1H-indole-2-carboxylic acid

Product 1

HCID 66850586HCID 66850586, compoundYield 594.7%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

0.77 g (4.02 mmol) of N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (EDAC) and 0.54 g (4.02 mmol) of 1-hydroxybenzotriazole (HOBT) are added to a solution, stirred at 20° C. under an inert atmosphere, of 1.4 g (4.02 mmol) of 5-bromo-1-[(3-fluorophenyl)methyl]-1H-indole-2-carboxylic acid, prepared in stage 17.2, in 20 ml of DMF. The reaction mixture is stirred at ambient temperature for 20 minutes. 0.66 g (4.42 mmol) of 3-amino-6-(azetidin-1-yl)pyridine, prepared according to the protocol described in stage 1.6, is subsequently added to the reaction mixture. After stirring at 20° C. for 18 hours, the reaction mixture is poured into a mixture of 50 ml of water and 50 ml of ethyl acetate. The resulting mixture is separated by settling out and the aqueous phase is extracted with 20 ml of ethyl acetate. The combined organic phases are washed three times with 30 ml of water, dried over sodium sulphate and then concentrated under reduced pressure. The isolated product is subsequently precipitated, then washed with isopropyl ether at reflux, filtered under hot conditions, and then dried under reduced pressure. 11.46 g of the expected product are thus isolated.

Workup

  1. additionis subsequently added to the reaction mixture
  2. stirringAfter stirring at 20° C. for 18 hours
  3. customThe resulting mixture is separated
  4. extractionthe aqueous phase is extracted with 20 ml of ethyl acetate
  5. washThe combined organic phases are washed three times with 30 ml of water
  6. dry with materialdried over sodium sulphate
  7. concentrationconcentrated under reduced pressure
  8. customThe isolated product is subsequently precipitated
  9. washwashed with isopropyl ether
  10. temperatureat reflux
  11. filtrationfiltered under hot conditions
  12. customdried under reduced pressure

Sources & evidence

ORD record
ord-16b410439caa4fc0b68d50d5e5b78b5a
Source dataset
uspto-grants-2013_03
Patent number
US08399491B2

Reaction notes

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