Ammonium Hydroxide → 2-[2-(7-[2-Methoxy-1-(methoxymethyl)ethoxy]-5-{[6-(methylsulfonyl)pyridin-3-yl]oxy}-1H-indol-2-yl)-4,5-dihydro-1,3-thiazol-5-yl]acetamide

HRID 1188998Notes

Reaction equation

HRID 1188998 reaction equation
[CH3:1][O:2][CH2:3][CH:4]([CH2:35][O:36][CH3:37])[O:5][C:6]1[CH:7]=[C:8]([O:24][C:25]2[CH:26]=[N:27][C:28]([S:31]([CH3:34])(=[O:33])=[O:32])=[CH:29][CH:30]=2)[CH:9]=[C:10]2[C:14]=1[NH:13][C:12]([C:15]1[S:16][CH:17]([CH2:20][C:21](O)=[O:22])[CH2:18][N:19]=1)=[CH:11]2.Cl.C([N:41]=C=NCCCN(C)C)C.ON1C2C=CC=CC=2N=N1.[OH-].[NH4+]>CN(C)C=O>[CH3:37][O:36][CH2:35][CH:4]([CH2:3][O:2][CH3:1])[O:5][C:6]1[CH:7]=[C:8]([O:24][C:25]2[CH:26]=[N:27][C:28]([S:31]([CH3:34])(=[O:32])=[O:33])=[CH:29][CH:30]=2)[CH:9]=[C:10]2[C:14]=1[NH:13][C:12]([C:15]1[S:16][CH:17]([CH2:20][C:21]([NH2:41])=[O:22])[CH2:18][N:19]=1)=[CH:11]2

Participants

6

Reactant 4

HCID 14923Ammonium HydroxideHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 66896936[2-(7-[2-Methoxy-1-(methoxymethyl)ethoxy]-5-{[6-(methylsulfonyl)pyridin-3-yl]oxy}-1H-indol-2-yl)-4,5-dihydro-1,3-thiazol-5-yl]acetic acid

Product 1

HCID 668983672-[2-(7-[2-Methoxy-1-(methoxymethyl)ethoxy]-5-{[6-(methylsulfonyl)pyridin-3-yl]oxy}-1H-indol-2-yl)-4,5-dihydro-1,3-thiazol-5-yl]acetamideYield 74%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
50 °C

Procedure

A mixture of [2-(7-[2-methoxy-1-(methoxymethyl)ethoxy]-5-{[6-(methylsulfonyl)pyridin-3-yl]oxy}-1H-indol-2-yl)-4,5-dihydro-1,3-thiazol-5-yl]acetic acid (190 mg), N-ethyl-N′-(3-dimethylaminopropyl)carbodiimide hydrochloride (133 mg), 1-hydroxybenzotriazole (93 mg) and N,N-dimethylformamide (5 mL) was stirred at 50° C. for 20 min. After cooling to room temperature, 10% aqueous ammonium hydroxide solution (0.5 mL) was added to the mixture and the mixture was stirred at room temperature for 14 h. The mixture was concentrated under reduced pressure. The residue was dissolved in water and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over magnesium sulfate, filtered and concentrated. The residual oil was crystallized from ethyl acetate. The resulting crystals were washed with diethyl. ether. The crystals were recrystallized from acetonitrile to give the title compound (139 mg, 74%) as colorless crystals. MS 549 (MH+). mp 172-173° C.

Workup

  1. temperatureAfter cooling to room temperature
  2. stirringthe mixture was stirred at room temperature for 14 h
  3. concentrationThe mixture was concentrated under reduced pressure
  4. dissolutionThe residue was dissolved in water
  5. extractionthe mixture was extracted with ethyl acetate
  6. washThe organic layer was washed with saturated brine
  7. dry with materialdried over magnesium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe residual oil was crystallized from ethyl acetate
  11. washThe resulting crystals were washed with diethyl
  12. customThe crystals were recrystallized from acetonitrile

Sources & evidence

ORD record
ord-808def91a06147bbab81fa15f357309d
Source dataset
uspto-grants-2014_03
Patent number
US08673942B2

Reaction notes

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