Ammonia → 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 1042157Notes

Reaction equation

HRID 1042157 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](O)=[O:35])[CH2:31][N:32]=2)=[CH:15]3)=[N:9][CH:10]=1)(=[O:4])=[O:3].[N:37]1(O)C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.N>O.CN(C)C=O>[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[CH2:23][CH2:24][O:25][CH2:26][CH2:27]4)[CH:20]=2)[NH:17][C:16]([C:28]2[S:29][CH:30]([CH2:33][C:34]([NH2:37])=[O:35])[CH2:31][N:32]=2)=[CH:15]3)=[N:9][CH:10]=1)(=[O:4])=[O:3]

Participants

7

Reactant 4

HCID 222AmmoniaHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 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 580810702-{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 62%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
50 °C

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 (210 mg), 1H-1,2,3-benzotriazol-1-ol (80 mg), N-[3-(dimethylamino)propyl]-N′-ethylcarbodiimide hydrochloride (120 mg) and N,N-dimethylformamide (5 mL) was stirred at 50° C. for 30 min and cooled to 0° C. 10% Aqueous ammonia (1 mL) was added to the mixture, and the mixture was stirred at room temperature for 2.5 days. To the reaction mixture was added water and the mixture was extracted with ethyl acetate. The organic layer was washed successively with saturated aqueous sodium hydrogen carbonate and saturated brine, dried over magnesium sulfate, and subjected to silica gel short column chromatography (eluted with ethyl acetate-methanol (95/5, volume ratio)) to give pale-yellow crystals. The crystals were recrystallized from acetone-hexane to give the title compound (130 mg, yield 62%) as pale-yellow prism crystals.

Workup

  1. temperaturecooled to 0° C
  2. stirringthe mixture was stirred at room temperature for 2.5 days
  3. extractionthe mixture was extracted with ethyl acetate
  4. washThe organic layer was washed successively with saturated aqueous sodium hydrogen carbonate and saturated brine
  5. dry with materialdried over magnesium sulfate
  6. washsubjected to silica gel short column chromatography (eluted with ethyl acetate-methanol (95/5, volume ratio))
  7. customto give pale-yellow crystals
  8. customThe crystals were recrystallized from acetone-hexane

Sources & evidence

ORD record
ord-8ad81bc286c74b738c197f667c7a0668
Source dataset
uspto-grants-2013_10
Patent number
US08557805B2

Reaction notes

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