Ammonia → HCID 67118739, compound

HRID 1189042Notes

Reaction equation

HRID 1189042 reaction equation
[F:1][C:2]1[C:10]([O:11][CH2:12][CH2:13][O:14][CH3:15])=[C:9]2[C:5]([CH:6]=[C:7]([C:16]3[S:17][CH:18]([CH2:21][C:22]([OH:24])=O)[CH2:19][N:20]=3)[NH:8]2)=[CH:4][C:3]=1[O:25][C:26]1[CH:27]=[N:28][C:29]([S:32]([CH3:35])(=[O:34])=[O:33])=[CH:30][CH:31]=1.O[N:37]1C2C=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C.N>CN(C)C=O>[F:1][C:2]1[C:10]([O:11][CH2:12][CH2:13][O:14][CH3:15])=[C:9]2[C:5]([CH:6]=[C:7]([C:16]3[S:17][CH:18]([CH2:21][C:22]([NH2:37])=[O:24])[CH2:19][N:20]=3)[NH:8]2)=[CH:4][C:3]=1[O:25][C:26]1[CH:27]=[N:28][C:29]([S:32]([CH3:35])(=[O:34])=[O:33])=[CH:30][CH:31]=1

Participants

6

Reactant 4

HCID 222AmmoniaHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 67118649HCID 67118649, compound

Product 1

HCID 67118739HCID 67118739, compoundYield 62.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To an ice-cooled and stirred mixture of {2-[6-fluoro-7-(2-methoxyethoxy)-5-{[6-(methylsulfonyl)pyridin-3-yl]oxy}-1H-indol-2-yl]-4,5-dihydro-1,3-thiazol-5-yl}acetic acid (135 mg) in N,N-dimethylformamide (7 mL) were added 1-hydroxybenzotriazole (70 mg) and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (100 mg). After stirring at 4° C. to room temperature for 15 h, the reaction mixture was cooled on an ice bath and 10% aqueous ammonia solution (1.0 mL) was added thereto. The mixture was stirred at room temperature for 5 h and partitioned between ethyl acetate and water. The organic layer was washed with aqueous sodium hydrogen carbonate solution and brine, dried (MgSO4), filtered, and concentrated to give light yellow crystals, which were recrystallized from tetrahydrofuran-ethyl acetate to give the title compound (84 mg) as pale yellow crystals. MS 523 (MH+). mp 143-144° C.

Workup

  1. stirringAfter stirring at 4° C. to room temperature for 15 h
  2. temperaturethe reaction mixture was cooled on an ice bath
  3. stirringThe mixture was stirred at room temperature for 5 h
  4. custompartitioned between ethyl acetate and water
  5. washThe organic layer was washed with aqueous sodium hydrogen carbonate solution and brine
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customto give light yellow crystals, which
  10. customwere recrystallized from tetrahydrofuran-ethyl acetate

Sources & evidence

ORD record
ord-8bda30fb79864e188aa422b1cac4df6c
Source dataset
uspto-grants-2014_03
Patent number
US08673942B2

Reaction notes

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