Ammonia → 5-{[6-(Methylsulfonyl)pyridin-3-yl]oxy}-7-(tetrahydro-2H-pyran-4-yloxy)-1H-indole-2-carboxamide

HRID 1042125Notes

Reaction equation

HRID 1042125 reaction equation
[CH3:1][S:2]([C:5]1[N:10]=[CH:9][C:8]([O:11][C:12]2[CH:13]=[C:14]3[C:18](=[C:19]([O:21][CH:22]4[CH2:27][CH2:26][O:25][CH2:24][CH2:23]4)[CH:20]=2)[NH:17][C:16]([C:28]([OH:30])=O)=[CH:15]3)=[CH:7][CH:6]=1)(=[O:4])=[O:3].O.O[N:33]1C2C=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C.N.Cl>CN(C)C=O>[CH3:1][S:2]([C:5]1[N:10]=[CH:9][C:8]([O:11][C:12]2[CH:13]=[C:14]3[C:18](=[C:19]([O:21][CH:22]4[CH2:27][CH2:26][O:25][CH2:24][CH2:23]4)[CH:20]=2)[NH:17][C:16]([C:28]([NH2:33])=[O:30])=[CH:15]3)=[CH:7][CH:6]=1)(=[O:3])=[O:4]

Participants

7

Reactant 5

HCID 222AmmoniaHCID 313Hydrochloric AcidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 667259795-{[6-(Methylsulfonyl)pyridin-3-yl]oxy}-7-(tetrahydro-2H-pyran-4-yloxy)-1H-indole-2-carboxylic acid

Product 1

HCID 667260845-{[6-(Methylsulfonyl)pyridin-3-yl]oxy}-7-(tetrahydro-2H-pyran-4-yloxy)-1H-indole-2-carboxamideYield 45.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 5-{[6-(methylsulfonyl)pyridin-3-yl]oxy}-7-(tetrahydro-2H-pyran-4-yloxy)-1H-indole-2-carboxylic acid (3 g) in N,N-dimethylformamide (20 mL) were added 1-hydroxybenzotriazole monohydrate (1.6 g), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (2 g), and 10% aqueous ammonia (27 mL), and the mixture was stirred at room temperature for 1 hr. 1N HCl was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium hydrogen carbonate solution and saturated brine, dried over magnesium sulfate, filtered and concentrated under reduced pressure. The obtained crude product was crystallized from diethyl ether to give the title compound (1.35 g, yield 45%) as yellow powder.

Workup

  1. extractionthe mixture was extracted with ethyl acetate
  2. washThe organic layer was washed with saturated aqueous sodium hydrogen carbonate solution and saturated brine
  3. dry with materialdried over magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe obtained crude product
  7. customwas crystallized from diethyl ether

Sources & evidence

ORD record
ord-bffa31973c164cc0aee002d60ce70e3c
Source dataset
uspto-grants-2013_10
Patent number
US08557805B2

Reaction notes

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