1-Hydroxybenzotriazole → 2-[2-(7-Methyl-5-{[6-(methylsulfonyl)pyridin-3-yl]oxy}-1H-indol-2-yl)-4,5-dihydro-1,3-thiazol-5-yl]-N-methylacetamide

HRID 1042201Notes

Reaction equation

HRID 1042201 reaction equation
Cl.CN.[CH3:4][C:5]1[CH:6]=[C:7]([O:23][C:24]2[CH:25]=[N:26][C:27]([S:30]([CH3:33])(=[O:32])=[O:31])=[CH:28][CH:29]=2)[CH:8]=[C:9]2[C:13]=1[NH:12][C:11]([C:14]1[S:15][CH:16]([CH2:19][C:20]([OH:22])=O)[CH2:17][N:18]=1)=[CH:10]2.O[N:35]1[C:39]2C=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C>O.CN(C)C=O.C(N(CC)CC)C>[CH3:4][C:5]1[CH:6]=[C:7]([O:23][C:24]2[CH:25]=[N:26][C:27]([S:30]([CH3:33])(=[O:31])=[O:32])=[CH:28][CH:29]=2)[CH:8]=[C:9]2[C:13]=1[NH:12][C:11]([C:14]1[S:15][CH:16]([CH2:19][C:20]([NH:35][CH3:39])=[O:22])[CH2:17][N:18]=1)=[CH:10]2

Participants

8

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 6364545Methylamine hydrochlorideHCID 58081062[2-(7-Methyl-5-{[6-(methylsulfonyl)pyridin-3-yl]oxy}-1H-indol-2-yl)-4,5-dihydro-1,3-thiazol-5-yl]acetic acid

Product 1

HCID 667261552-[2-(7-Methyl-5-{[6-(methylsulfonyl)pyridin-3-yl]oxy}-1H-indol-2-yl)-4,5-dihydro-1,3-thiazol-5-yl]-N-methylacetamideYield 85%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8471TriethylamineSolvent

Procedure

To a mixed solution of methylamine hydrochloride (120 mg), triethylamine (0.24 mL) and N,N-dimethylformamide (20 mL) were added [2-(7-methyl-5-{[6-(methylsulfonyl)pyridin-3-yl]oxy}-1H-indol-2-yl)-4,5-dihydro-1,3-thiazol-5-yl]acetic acid (500 mg), 1-hydroxybenzotriazole (230 mg), and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (330 mg) under ice-cooling, and the mixture was stirred from under ice-cooling to room temperature for 2 days. Water was added to the reaction solution, and the mixture was extracted with ethyl acetate. The organic layer was washed with aqueous sodium hydrogen carbonate solution and saturated brine, dried over magnesium sulfate, filtered and concentrated under reduced pressure. The obtained residue was subjected to silica gel column chromatography (ethyl acetate:methanol=100:0 to 85:15, volume ratio), and the obtained colorless oil was crystallized from ethyl acetate-hexane to give the title compound (436 mg, yield 85%) as colorless crystals.

Workup

  1. temperaturecooling
  2. extractionthe mixture was extracted with ethyl acetate
  3. washThe organic layer was washed with aqueous sodium hydrogen carbonate solution and saturated brine
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customthe obtained colorless oil was crystallized from ethyl acetate-hexane

Sources & evidence

ORD record
ord-652057773a724aa297e4b3e827d398b2
Source dataset
uspto-grants-2013_10
Patent number
US08557805B2

Reaction notes

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