1,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride → 2-[2-(7-Methoxy-5-{[6-(methylsulfonyl)pyridin-3-yl]oxy}-1H-indol-2-yl)-4,5-dihydro-1,3-thiazol-5-yl]acetamide

HRID 1188994Notes

Reaction equation

HRID 1188994 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([O:21][C:22]2[CH:23]=[N:24][C:25]([S:28]([CH3:31])(=[O:30])=[O:29])=[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](O)=[O:19])[CH2:15][N:16]=1)=[CH:8]2.Cl.C([N:35]=C=NCCCN(C)C)C.[NH4+].ON1C2C=CC=CC=2N=N1>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]([S:28]([CH3:31])(=[O:29])=[O: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]([NH2:35])=[O:19])[CH2:15][N:16]=1)=[CH:8]2

Participants

5

Reactant 3

HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 220338091-Hydroxybenzotriazole, ammonium saltHCID 67118501[2-(7-Methoxy-5-{[6-(methylsulfonyl)pyridin-3-yl]oxy}-1H-indol-2-yl)-4,5-dihydro-1,3-thiazol-5-yl]acetic acid

Product 1

HCID 671188142-[2-(7-Methoxy-5-{[6-(methylsulfonyl)pyridin-3-yl]oxy}-1H-indol-2-yl)-4,5-dihydro-1,3-thiazol-5-yl]acetamideYield 64.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of [2-(7-methoxy-5-{[6-(methylsulfonyl)pyridin-3-yl]oxy}-1H-indol-2-yl)-4,5-dihydro-1,3-thiazol-5-yl]acetic acid (90 mg), N-ethyl-N′-(3-dimethylaminopropyl)carbodiimide hydrochloride (75 mg), 1-hydroxybenzotriazole ammonium salt (59 mg) and N,N-dimethylformamide (4 mL) was stirred at room temperature for 12 h. The mixture was concentrated under reduced pressure. The residue was dissolved in water and the mixture was extracted with ethyl acetate-tetrahydrofuran. The organic layer was washed with saturated brine, dried over magnesium sulfate, filtered and concentrated. The residual oil was crystallized from acetonitrile and the crystals were washed with acetonitrile-diethyl ether. The crystals were recrystallized from ethanol to give the title compound (58 mg, 64%) as off-white crystals. MS 461 (MH+). mp 225-227° 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-tetrahydrofuran
  4. washThe organic layer was washed with saturated brine
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residual oil was crystallized from acetonitrile
  9. washthe crystals were washed with acetonitrile-diethyl ether
  10. customThe crystals were recrystallized from ethanol

Sources & evidence

ORD record
ord-8087e51208ca4df787092498d9dee9a2
Source dataset
uspto-grants-2014_03
Patent number
US08673942B2

Reaction notes

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