Water → 2-{2-[5-{[6-(Methoxymethyl)pyridin-3-yl]oxy}-7-(tetrahydro-2H-pyran-4-yloxy)-1H-indol-2-yl]-4,5-dihydro-1,3-thiazol-5-yl}ethanol

HRID 1042149Notes

Reaction equation

HRID 1042149 reaction equation
C([O:3][C:4](=O)[CH2:5][CH:6]1[S:10][C:9]([C:11]2[NH:12][C:13]3[C:18]([CH:19]=2)=[CH:17][C:16]([O:20][C:21]2[CH:22]=[N:23][C:24]([CH2:27][O:28][CH3:29])=[CH:25][CH:26]=2)=[CH:15][C:14]=3[O:30][CH:31]2[CH2:36][CH2:35][O:34][CH2:33][CH2:32]2)=[N:8][CH2:7]1)C.[BH4-].[Li+].O>O1CCCC1.CO.CCCCCC.C(OCC)(=O)C>[CH3:29][O:28][CH2:27][C:24]1[N:23]=[CH:22][C:21]([O:20][C:16]2[CH:17]=[C:18]3[C:13](=[C:14]([O:30][CH:31]4[CH2:36][CH2:35][O:34][CH2:33][CH2:32]4)[CH:15]=2)[NH:12][C:11]([C:9]2[S:10][CH:6]([CH2:5][CH2:4][OH:3])[CH2:7][N:8]=2)=[CH:19]3)=[CH:26][CH:25]=1

Participants

8

Reactant 3

HCID 962WaterHCID 4148881Lithium borohydrideHCID 58081032ethyl{2-[5-{[6-(methoxymethyl)pyridin-3-yl]oxy}-7-(tetrahydro-2H-pyran-4-yloxy)-1H-indol-2-yl]-4,5-dihydro-1,3-thiazol-5-yl}acetate

Product 1

HCID 580810412-{2-[5-{[6-(Methoxymethyl)pyridin-3-yl]oxy}-7-(tetrahydro-2H-pyran-4-yloxy)-1H-indol-2-yl]-4,5-dihydro-1,3-thiazol-5-yl}ethanolYield 26.5%

Reagents, catalysts & solvents 4

HCID 887MethanolSolvent2×HCID 8028TetrahydrofuranSolventHCID 8058HexaneSolvent2×HCID 8857Ethyl AcetateSolvent2×

Procedure

To a solution of ethyl{2-[5-{[6-(methoxymethyl)pyridin-3-yl]oxy}-7-(tetrahydro-2H-pyran-4-yloxy)-1H-indol-2-yl]-4,5-dihydro-1,3-thiazol-5-yl}acetate (500 mg) in tetrahydrofuran (10 mL) and methanol (15 mL) was added lithium tetrahydroborate (80 mg) at room temperature 3 times at 30 min intervals, 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 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 further to silica gel column chromatography (methanol:ethyl acetate:hexane=0:0:100 to 10:90:0, volume ratio). The obtained crude product was purified by preparative HPLC to give the title compound (122 mg, yield 26%) as a colorless amorphous solid.

Workup

  1. extractionthe mixture was extracted with ethyl acetate
  2. washThe organic layer was washed with saturated brine
  3. dry with materialdried over magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe obtained crude product
  7. customThe obtained crude product
  8. customwas purified by preparative HPLC

Sources & evidence

ORD record
ord-4ca01feb89f54223994b76e6590e601e
Source dataset
uspto-grants-2013_10
Patent number
US08557805B2

Reaction notes

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