Ammonia → HCID 58081033, compound

HRID 1042167Notes

Reaction equation

HRID 1042167 reaction equation
[CH3:1][S:2]([CH2:5][C:6]1[N:11]=[CH:10][C:9]([O:12][C:13]2[CH:14]=[C:15]3[C:19](=[C:20]([O:22][CH:23]4[CH2:28][CH2:27][O:26][CH2:25][CH2:24]4)[CH:21]=2)[NH:18][C:17]([C:29]2[S:30][CH:31]([CH2:34][C:35](O)=[O:36])[CH2:32][N:33]=2)=[CH:16]3)=[CH:8][CH:7]=1)(=[O:4])=[O:3].O.O[N:40]1C2C=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C.N>CN(C)C=O.CCCCCC.C(OCC)(=O)C.O>[CH3:1][S:2]([CH2:5][C:6]1[N:11]=[CH:10][C:9]([O:12][C:13]2[CH:14]=[C:15]3[C:19](=[C:20]([O:22][CH:23]4[CH2:24][CH2:25][O:26][CH2:27][CH2:28]4)[CH:21]=2)[NH:18][C:17]([C:29]2[S:30][CH:31]([CH2:34][C:35]([NH2:40])=[O:36])[CH2:32][N:33]=2)=[CH:16]3)=[CH:8][CH:7]=1)(=[O:4])=[O:3]

Participants

9

Reactant 4

HCID 222AmmoniaHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 58081010HCID 58081010, compound

Product 1

HCID 58081033HCID 58081033, compoundYield 68.1%

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8058HexaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of {2-[5-({6-[(methylsulfonyl)methyl]pyridin-3-yl}oxy)-7-(tetrahydro-2H-pyran-4-yloxy)-1H-indol-2-yl]-4,5-dihydro-1,3-thiazol-5-yl}acetic acid (200 mg) in N,N-dimethylformamide (5 mL) were added 1-hydroxybenzotriazole monohydrate (84 mg), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (105 mg), and 25% aqueous ammonia (2 mL), and the mixture was stirred at room temperature for 1 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 (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 (136 mg, yield 68%) 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
  8. customThe obtained crystals were recrystallized from ethyl acetate and diethyl ether

Sources & evidence

ORD record
ord-8d0eaac773714a62863fe50483f64faf
Source dataset
uspto-grants-2013_10
Patent number
US08557805B2

Reaction notes

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