Water → 2-[2-(7-[2-Methoxy-1-(methoxymethyl)ethoxy]-5-{[6-(methylsulfonyl)pyridin-3-yl]oxy}-1H-indol-2-yl)-4,5-dihydro-1,3-thiazol-5-yl]ethanol

HRID 1189000Notes

Reaction equation

HRID 1189000 reaction equation
[CH3:1][O:2][CH2:3][CH:4]([CH2:37][O:38][CH3:39])[O:5][C:6]1[CH:7]=[C:8]([O:26][C:27]2[CH:28]=[N:29][C:30]([S:33]([CH3:36])(=[O:35])=[O:34])=[CH:31][CH:32]=2)[CH:9]=[C:10]2[C:14]=1[NH:13][C:12]([C:15]1[S:16][CH:17]([CH2:20][C:21](OCC)=[O:22])[CH2:18][N:19]=1)=[CH:11]2.[BH4-].[Li+].O>O1CCCC1.CO>[CH3:1][O:2][CH2:3][CH:4]([CH2:37][O:38][CH3:39])[O:5][C:6]1[CH:7]=[C:8]([O:26][C:27]2[CH:28]=[N:29][C:30]([S:33]([CH3:36])(=[O:34])=[O:35])=[CH:31][CH:32]=2)[CH:9]=[C:10]2[C:14]=1[NH:13][C:12]([C:15]1[S:16][CH:17]([CH2:20][CH2:21][OH:22])[CH2:18][N:19]=1)=[CH:11]2

Participants

6

Reactant 3

HCID 962WaterHCID 4148881Lithium borohydrideHCID 66898144Ethyl [2-(7-[2-methoxy-1-(methoxymethyl)ethoxy]-5-{[6-(methylsulfonyl)pyridin-3-yl]oxy}-1H-indol-2-yl)-4,5-dihydro-1,3-thiazol-5-yl]acetate

Product 1

HCID 671185452-[2-(7-[2-Methoxy-1-(methoxymethyl)ethoxy]-5-{[6-(methylsulfonyl)pyridin-3-yl]oxy}-1H-indol-2-yl)-4,5-dihydro-1,3-thiazol-5-yl]ethanolYield 75%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

Ethyl [2-(7-[2-methoxy-1-(methoxymethyl)ethoxy]-5-{[6-(methylsulfonyl)pyridin-3-yl]oxy}-1H-indol-2-yl)-4,5-dihydro-1,3-thiazol-5-yl]acetate (220 mg) was dissolved in a mixture of tetrahydrofuran (2 mL) and methanol (1 mL). Lithium borohydride (41 mg) was added to the mixture at 0° C. and the mixture was stirred at room temperature for 6.5 h. Water was added to the mixture and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over magnesium sulfate, filtered and concentrated. The residue was purified by silica gel column chromatography (methanol/ethyl acetate/hexane=0/40/60 to 15/85/0, volume ratio) to give an orange oil. The oil was crystallized from acetonitrile. The crystals were recrystallized from acetonitrile-diethyl ether to give the title compound (105 mg, 75%) as colorless crystals. MS 536 (MH+). mp 69-71° C.

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
  6. customThe residue was purified by silica gel column chromatography (methanol/ethyl acetate/hexane=0/40/60 to 15/85/0, volume ratio)
  7. customto give an orange oil
  8. customThe oil was crystallized from acetonitrile
  9. customThe crystals were recrystallized from acetonitrile-diethyl ether

Sources & evidence

ORD record
ord-163e47107f7b469a9acd1fd231cf8242
Source dataset
uspto-grants-2014_03
Patent number
US08673942B2

Reaction notes

Loading…