Ammonium Hydroxide → HCID 67118604, compound

HRID 1189009Notes

Reaction equation

HRID 1189009 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([O:21][C:22]2[CH:23]=[N:24][C:25]([CH2:28][O:29][CH3:30])=[CH:26][CH:27]=2)[CH:6]=[C:7]2[C:11]=1[NH:10][C:9]([C:12]1[S:13][CH:14]([CH2:17][C:18]([OH:20])=O)[CH2:15][N:16]=1)=[CH:8]2.Cl.C([N:34]=C=NCCCN(C)C)C.O.ON1C2C=CC=CC=2N=N1.[OH-].[NH4+]>CN(C)C=O>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([O:21][C:22]2[CH:23]=[N:24][C:25]([CH2:28][O:29][CH3:30])=[CH:26][CH:27]=2)[CH:6]=[C:7]2[C:11]=1[NH:10][C:9]([C:12]1[S:13][CH:14]([CH2:17][C:18]([NH2:34])=[O:20])[CH2:15][N:16]=1)=[CH:8]2

Participants

6

Reactant 4

HCID 14923Ammonium HydroxideHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 67118679HCID 67118679, compound

Product 1

HCID 67118604HCID 67118604, compoundYield 43%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of [2-(7-methoxy-5-{[6-(methoxymethyl)pyridin-3-yl]oxy}-1H-indol-2-yl)-4,5-dihydro-1,3-thiazol-5-yl]acetic acid (160 mg), N-ethyl-N′-(3-dimethylaminopropyl)carbodiimide hydrochloride (144 mg), 1-hydroxybenzotriazole monohydrate (115 mg), 25% aqueous ammonium hydroxide solution (1 mL) and N,N-dimethylformamide (8 mL) was stirred at room temperature for 3.5 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 residue was purified by basic silica gel column chromatography (methanol/ethyl acetate=0/100 to 8/92, volume ratio) to give a white amorphous solid. The amorphous solid was crystallized from ethyl acetate-diethyl ether to give white crystals. The crystals were recrystallized from ethyl acetate-hexane to give the title compound (68 mg, 43%) as colorless crystals. MS 427 (MH+). mp 135-136° C.

Workup

  1. concentrationThe mixture was concentrated under reduced pressure
  2. dissolutionThe residue was dissolved in water
  3. extractionthe mixture was extracted with ethyl acetate
  4. washThe organic layer was washed with saturated brine
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was purified by basic silica gel column chromatography (methanol/ethyl acetate=0/100 to 8/92, volume ratio)
  9. customto give a white amorphous solid
  10. customThe amorphous solid was crystallized from ethyl acetate-diethyl ether
  11. customto give white crystals
  12. customThe crystals were recrystallized from ethyl acetate-hexane

Sources & evidence

ORD record
ord-7f29de4cc86f4b21855fb05921c5fd7f
Source dataset
uspto-grants-2014_03
Patent number
US08673942B2

Reaction notes

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