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

HRID 1042203Notes

Reaction equation

HRID 1042203 reaction equation
[CH3:1][C:2]1[CH:3]=[C:4]([O:20][C:21]2[CH:22]=[N:23][C:24]([S:27]([CH3:30])(=[O:29])=[O:28])=[CH:25][CH:26]=2)[CH:5]=[C:6]2[C:10]=1[NH:9][C:8]([C:11]1[S:12][CH:13]([CH2:16][C:17]([OH:19])=O)[CH2:14][N:15]=1)=[CH:7]2.[NH2:31][CH2:32][C@@H:33]([OH:35])[CH3:34].ON1C2C=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C>CN(C)C=O.O>[OH:35][C@@H:33]([CH3:34])[CH2:32][NH:31][C:17](=[O:19])[CH2:16][CH:13]1[S:12][C:11]([C:8]2[NH:9][C:10]3[C:6]([CH:7]=2)=[CH:5][C:4]([O:20][C:21]2[CH:22]=[N:23][C:24]([S:27]([CH3:30])(=[O:29])=[O:28])=[CH:25][CH:26]=2)=[CH:3][C:2]=3[CH3:1])=[N:15][CH2:14]1

Participants

7

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 7311736(S)-(+)-1-Aminopropan-2-olHCID 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 66726080N-[(2S)-2-Hydroxypropyl]-2-[2-(7-methyl-5-{[6-(methylsulfonyl)pyridin-3-yl]oxy}-1H-indol-2-yl)-4,5-dihydro-1,3-thiazol-5-yl]acetamideYield 68%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of [2-(7-methyl-5-{[6-(methylsulfonyl)pyridin-3-yl]oxy}-1H-indol-2-yl)-4,5-dihydro-1,3-thiazol-5-yl]acetic acid (300 mg) and (S)-(+)-1-amino-2-propanol (78 mg) in N,N-dimethylformamide (20 mL)were added 1-hydroxybenzotriazole (137 mg) and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (194 mg) under ice-cooling, and the mixture was stirred under ice-cooling and then at room temperature for 15 hr. 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 pale-yellow crystals were recrystallized from tetrahydrofuran-ethyl acetate to give the title compound (230 mg, yield 68%) as colorless crystals.

Workup

  1. temperaturecooling
  2. temperaturecooling
  3. extractionthe mixture was extracted with ethyl acetate
  4. washThe organic layer was washed with aqueous sodium hydrogen carbonate solution and saturated brine
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe obtained pale-yellow crystals were recrystallized from tetrahydrofuran-ethyl acetate

Sources & evidence

ORD record
ord-2700a00163144d48bd25919b19d21b9d
Source dataset
uspto-grants-2013_10
Patent number
US08557805B2

Reaction notes

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