Hydrochloric Acid → N-methyl-2-{2-[5-{[6-(Methylsulfonyl)pyridin-3-yl]oxy}-7-(tetrahydro-2H-pyran-4-yloxy)-1H-indol-2-yl]-4,5-dihydro-1,3-thiazol-5-yl}acetamide

HRID 1042173Notes

Reaction equation

HRID 1042173 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](=[C:19]([O:21][CH:22]4[CH2:27][CH2:26][O:25][CH2:24][CH2:23]4)[CH:20]=2)[NH:17][C:16]([C:28]2[S:29][CH:30]([CH2:33][C:34](O)=[O:35])[CH2:31][N:32]=2)=[CH:15]3)=[CH:7][CH:6]=1)(=[O:4])=[O:3].O.O[N:39]1[C:43]2C=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C.Cl.CN.Cl>CN(C)C=O.CCCCCC.C(OCC)(=O)C.C(N(CC)CC)C>[CH3:43][NH:39][C:34](=[O:35])[CH2:33][CH:30]1[S:29][C:28]([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][C:19]=3[O:21][CH:22]2[CH2:27][CH2:26][O:25][CH2:24][CH2:23]2)=[N:32][CH2:31]1

Participants

10

Reactant 5

HCID 313Hydrochloric AcidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 6364545Methylamine hydrochlorideHCID 58081027(2-[5-{[6-(methylsulfonyl)pyridin-3-yl]oxy}-7-(tetrahydro-2H-pyran-4-yloxy)-1H-indol-2-yl]-4,5-dihydro-1,3-thiazol-5-yl]acetic acid

Product 1

HCID 66725923N-methyl-2-{2-[5-{[6-(Methylsulfonyl)pyridin-3-yl]oxy}-7-(tetrahydro-2H-pyran-4-yloxy)-1H-indol-2-yl]-4,5-dihydro-1,3-thiazol-5-yl}acetamideYield 31%

Reagents, catalysts & solvents 4

HCID 6228DimethylformamideSolventHCID 8058HexaneSolventHCID 8471TriethylamineSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of (2-[5-{[6-(methylsulfonyl)pyridin-3-yl]oxy}-7-(tetrahydro-2H-pyran-4-yloxy)-1H-indol-2-yl]-4,5-dihydro-1,3-thiazol-5-yl]acetic acid (365 mg) in N,N-dimethylformamide (5 mL) were added 1-hydroxybenzotriazole monohydrate (158 mg), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (198 mg), methylamine hydrochloride (70 mg), and triethylamine (0.144 mL), and the mixture was stirred at room temperature for 1 hr. 1N HCl 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 (ethyl acetate:hexane=0:100 to 100:0, volume ratio), and crystallized from acetonitrile. The obtained crystals were recrystallized from ethyl acetate and diethyl ether to give the title compound (115 mg, yield 31%) as white powder.

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
  8. customThe obtained crystals were recrystallized from ethyl acetate and diethyl ether

Sources & evidence

ORD record
ord-820d326cda3d456991bb8a40603e62d4
Source dataset
uspto-grants-2013_10
Patent number
US08557805B2

Reaction notes

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