1-Hydroxybenzotriazole → HCID 44199404, compound

HRID 1948787Notes

Reaction equation

HRID 1948787 reaction equation
Cl.CN(C)CCCN=C=NCC.ON1C2C=CC=CC=2N=N1.[CH3:23][Si:24]([CH3:46])([CH3:45])[C:25]1[CH:26]=[C:27]2[C:31](=[CH:32][CH:33]=1)[N:30]([CH2:34][C:35]1[CH:40]=[CH:39][CH:38]=[C:37]([F:41])[CH:36]=1)[C:29]([C:42](O)=[O:43])=[CH:28]2.[NH2:47][C:48]1[CH:49]=[N:50][C:51]([N:54]2[CH2:57][CH2:56][CH2:55]2)=[CH:52][CH:53]=1.C([O-])(O)=O.[Na+]>CN(C=O)C.CCOC(C)=O>[N:54]1([C:51]2[N:50]=[CH:49][C:48]([NH:47][C:42]([C:29]3[N:30]([CH2:34][C:35]4[CH:40]=[CH:39][CH:38]=[C:37]([F:41])[CH:36]=4)[C:31]4[C:27]([CH:28]=3)=[CH:26][C:25]([Si:24]([CH3:46])([CH3:23])[CH3:45])=[CH:33][CH:32]=4)=[O:43])=[CH:53][CH:52]=2)[CH2:57][CH2:56][CH2:55]1

Participants

8

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 516892Sodium BicarbonateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 552816836-(1-Azetidinyl)-3-pyridinamineHCID 581009535-trimethylsilyl-1-[(3-fluorophenyl)methyl]-1H-indole-2-carboxylic acid

Product 1

HCID 44199404HCID 44199404, compoundYield 33.8%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

98 mg (0.51 mmol) of N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (EDC) and 69 mg (0.51 mmol) of 1-hydroxybenzotriazole (HOBt) are added to a solution, stirred at 20° C. under an inert atmosphere, of 0.16 g (0.47 mmol) of 5-trimethylsilyl-1-[(3-fluorophenyl)methyl]-1H-indole-2-carboxylic acid, prepared according to the protocol described in stage 3.6, in 10 ml of DMF. The reaction mixture is stirred at ambient temperature for 15 minutes. 84 mg (0.56 mmol) of 3-amino-6-(azetidin-1-yl)pyridine, prepared according to the protocol described in stage 1.6, are subsequently added to the reaction mixture. After stirring at 20° C. for 16 h, the reaction mixture is poured into a mixture of 30 ml of a saturated aqueous solution of NaHCO3 and 30 ml of EtOAc. The aqueous phase is extracted with 20 ml of EtOAc. The combined organic phases are washed with 3×30 ml of water, dried over Na2SO4, and then concentrated under reduced pressure. The solid obtained after evaporation of the solvent under reduced pressure is washed with isopropyl ether at reflux, filtered under hot conditions and then dried under reduced pressure. 75 mg of the expected product are thus isolated.

Workup

  1. customprepared
  2. additionare subsequently added to the reaction mixture
  3. stirringAfter stirring at 20° C. for 16 h
  4. extractionThe aqueous phase is extracted with 20 ml of EtOAc
  5. washThe combined organic phases are washed with 3×30 ml of water
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated under reduced pressure
  8. customThe solid obtained
  9. customafter evaporation of the solvent under reduced pressure
  10. washis washed with isopropyl ether
  11. temperatureat reflux
  12. filtrationfiltered under hot conditions
  13. customdried under reduced pressure

Sources & evidence

ORD record
ord-8d154844497245c694bbf17327dfddd8
Source dataset
uspto-grants-2013_03
Patent number
US08399491B2

Reaction notes

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