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

HRID 1042158Notes

Reaction equation

HRID 1042158 reaction equation
[CH3:1][S:2]([C:5]1[CH:6]=[CH:7][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]2[S:29][CH:30]([CH2:33][C:34]([OH:36])=O)[CH2:31][N:32]=2)=[CH:15]3)=[N:9][CH:10]=1)(=[O:4])=[O:3].[N:37]1(O)[C:41]2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.Cl.CN.C(=O)([O-])O.[Na+]>CN(C)C=O.C(N(CC)CC)C>[CH3:41][NH:37][C:34](=[O:36])[CH2:33][CH:30]1[S:29][C:28]([C:16]2[NH:17][C:18]3[C:14]([CH:15]=2)=[CH:13][C:12]([O:11][C:8]2[CH:7]=[CH:6][C:5]([S:2]([CH3:1])(=[O:4])=[O:3])=[CH:10][N:9]=2)=[CH:20][C:19]=3[O:21][CH:22]2[CH2:23][CH2:24][O:25][CH2:26][CH2:27]2)=[N:32][CH2:31]1

Participants

8

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 516892Sodium BicarbonateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 6364545Methylamine hydrochlorideHCID 58081059{2-[5-{[5-(Methylsulfonyl)pyridin-2-yl]oxy}-7-(tetrahydro-2H-pyran-4-yloxy)-1H-indol-2-yl]-4,5-dihydro-1,3-thiazol-5-yl}acetic acid

Product 1

HCID 58081052N-Methyl-2-{2-[5-{[5-(methylsulfonyl)pyridin-2-yl]oxy}-7-(tetrahydro-2H-pyran-4-yloxy)-1H-indol-2-yl]-4,5-dihydro-1,3-thiazol-5-yl}acetamideYield 53.7%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8471TriethylamineSolvent

Procedure

A mixture of {2-[5-{[5-(methylsulfonyl)pyridin-2-yl]oxy}-7-(tetrahydro-2H-pyran-4-yloxy)-1H-indol-2-yl]-4,5-dihydro-1,3-thiazol-5-yl}acetic acid (200 mg), 1H-1,2,3-benzotriazol-1-ol (80 mg), N-[3-(dimethylamino)propyl]-N′-ethylcarbodiimidehydrochloride (110 mg), methylamine hydrochloride (50 mg), triethylamine (85 mg) and N,N-dimethylformamide (3 mL) was stirred at room temperature for 2.5 days. To the reaction mixture was added saturated aqueous sodium hydrogen carbonate and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over magnesium sulfate, filtered and concentrated under reduced pressure. The residue was subjected to silica gel chromatography, and eluted with ethyl acetate-methanol (100/0 to 95/5, volume ratio) to give colorless crystals. The crystals were recrystallized from acetone-hexane to give the title compound (110 mg, yield 52%) as colorless prism crystals.

Workup

  1. extractionthe mixture was extracted with ethyl acetate
  2. washThe organic layer was washed with saturated brine
  3. dry with materialdried over magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. washeluted with ethyl acetate-methanol (100/0 to 95/5, volume ratio)
  7. customto give colorless crystals
  8. customThe crystals were recrystallized from acetone-hexane

Sources & evidence

ORD record
ord-573bfca801b047878de321c87eb77ab9
Source dataset
uspto-grants-2013_10
Patent number
US08557805B2

Reaction notes

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