1-Hydroxybenzotriazole → 1-({2-[5-{[5-(Methylsulfonyl)pyridin-2-yl]oxy}-7-(tetrahydro-2H-pyran-4-yloxy)-1H-indol-2-yl]-4,5-dihydro-1,3-thiazol-5-yl}acetyl)azetidin-3-ol

HRID 1042159Notes

Reaction equation

HRID 1042159 reaction equation
[CH3:1][S:2]([C:5]1[CH:6]=[CH:7][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)=[N:9][CH:10]=1)(=[O:4])=[O:3].N1(O)C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.Cl.[NH:60]1[CH2:63][CH:62]([OH:64])[CH2:61]1>O.CN(C)C=O.C(N(CC)CC)C>[CH3:1][S:2]([C:5]1[CH:6]=[CH:7][C:8]([O:11][C:12]2[CH:13]=[C:14]3[C:18](=[C:19]([O:21][CH:22]4[CH2:23][CH2:24][O:25][CH2:26][CH2:27]4)[CH:20]=2)[NH:17][C:16]([C:28]2[S:29][CH:30]([CH2:33][C:34]([N:60]4[CH2:63][CH:62]([OH:64])[CH2:61]4)=[O:35])[CH2:31][N:32]=2)=[CH:15]3)=[N:9][CH:10]=1)(=[O:4])=[O:3]

Participants

8

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27592903-Hydroxyazetidine hydrochlorideHCID 58081059{2-[5-{[5-(Methylsulfonyl)pyridin-2-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 580810431-({2-[5-{[5-(Methylsulfonyl)pyridin-2-yl]oxy}-7-(tetrahydro-2H-pyran-4-yloxy)-1H-indol-2-yl]-4,5-dihydro-1,3-thiazol-5-yl}acetyl)azetidin-3-olYield 62%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8471TriethylamineSolvent

Procedure

A mixture of {2-[5-{[5-(methylsulfonyl)pyridin-2-yl]oxy}-7-(tetrahydro-2H-pyran-4-yloxy)-1H-indol-2-yl]-4,5-dihydro-1,3-thiazol-5-yl}acetic acid (190 mg), 1H-1,2,3-benzotriazol-1-ol (70 mg), N-[3-(dimethylamino)propyl]-N′-ethylcarbodiimide hydrochloride (100 mg), azetidin-3-ol hydrochloride (80 mg), triethylamine (80 mg) and N,N-dimethylformamide (3 mL) was stirred at room temperature for 15 hr. To the reaction mixture was added water and the mixture was extracted with ethyl acetate. The organic layer was washed successively with saturated aqueous sodium hydrogen carbonate and saturated brine, dried over magnesium sulfate, filtered and concentrated under reduced pressure. The residue was subjected to silica gel chromatography, and eluted with ethyl acetate-methanol (100/0 to 90/10, volume ratio) to give colorless crystals. The crystals were recrystallized from acetone-hexane to give the title compound (130 mg, yield 62%) as colorless prism crystals.

Workup

  1. extractionthe mixture was extracted with ethyl acetate
  2. washThe organic layer was washed successively with saturated aqueous sodium hydrogen carbonate and saturated brine
  3. dry with materialdried over magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. washeluted with ethyl acetate-methanol (100/0 to 90/10, volume ratio)
  7. customto give colorless crystals
  8. customThe crystals were recrystallized from acetone-hexane

Sources & evidence

ORD record
ord-1abd3e306c5246a1874172c92ec7845f
Source dataset
uspto-grants-2013_10
Patent number
US08557805B2

Reaction notes

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