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

HRID 1042188Notes

Reaction equation

HRID 1042188 reaction equation
[CH3:1][S:2]([C:5]1[N:10]=[CH:9][C:8]([O:11][C:12]2[CH:13]=[C:14]3[C:18](=[CH:19][CH:20]=2)[NH:17][C:16]([C:21]2[S:22][CH:23]([CH2:26][C:27]([OH:29])=O)[CH2:24][N:25]=2)=[CH:15]3)=[CH:7][CH:6]=1)(=[O:4])=[O:3].O.O[N:32]1[C:36]2C=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C.Cl.CN>CN(C)C=O.CCCCCC.C(OCC)(=O)C.CO.O.C(N(CC)CC)C>[CH3:36][NH:32][C:27](=[O:29])[CH2:26][CH:23]1[S:22][C:21]([C:16]2[NH:17][C:18]3[C:14]([CH:15]=2)=[CH:13][C:12]([O:11][C:8]2[CH:9]=[N:10][C:5]([S:2]([CH3:1])(=[O:3])=[O:4])=[CH:6][CH:7]=2)=[CH:20][CH:19]=3)=[N:25][CH2:24]1

Participants

11

Reactant 4

HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 6364545Methylamine hydrochlorideHCID 58081046HCID 58081046, compound

Product 1

HCID 46837102N-Methyl-2-[2-(5-{[6-(methylsulfonyl)pyridin-3-yl]oxy}-1H-indol-2-yl)-4,5-dihydro-1,3-thiazol-5-yl]acetamideYield 41.4%

Reagents, catalysts & solvents 6

HCID 887MethanolSolventHCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8058HexaneSolventHCID 8471TriethylamineSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of [2-(5-{[6-(methylsulfonyl)pyridin-3-yl]oxy}-1H-indol-2-yl)-4,5-dihydro-1,3-thiazol-5-yl]acetic acid (150 mg) in N,N-dimethylformamide (5 mL) were added 1-hydroxybenzotriazole monohydrate (80 mg), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (100 mg), methylamine hydrochloride (47 mg), and triethylamine (100 μL), and the mixture was stirred at room temperature for 15 hr. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium hydrogen carbonate solution and saturated brine, dried over magnesium sulfate, filtered and concentrated under reduced pressure. The obtained crude product was subjected to basic silica gel column chromatography (methanol:ethyl acetate:hexane=0:0:100 to 10:90:0, volume ratio) and crystallized from acetonitrile to give the title compound (64 mg, yield 41%) as white crystals.

Workup

  1. extractionthe mixture was extracted with ethyl acetate
  2. washThe organic layer was washed with saturated aqueous sodium hydrogen carbonate solution and saturated brine
  3. dry with materialdried over magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe obtained crude product
  7. customcrystallized from acetonitrile

Sources & evidence

ORD record
ord-096ba1c18a744d469a1d766b8d358278
Source dataset
uspto-grants-2013_10
Patent number
US08557805B2

Reaction notes

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