Ethylene Glycol → HCID 57970080, compound

HRID 1666631Notes

Reaction equation

HRID 1666631 reaction equation
[Cl:1][C:2]1[N:7]=[C:6]2[CH:8]=[CH:9][S:10][C:5]2=[C:4](Cl)[CH:3]=1.C(N(CC)CC)C.Cl.[CH3:20][S:21]([CH:24]1[CH2:29][CH2:28][NH:27][CH2:26][CH2:25]1)(=[O:23])=[O:22].C(O)CO>C(OCC)(=O)C.O1CCOCC1>[Cl:1][C:2]1[N:7]=[C:6]2[CH:8]=[CH:9][S:10][C:5]2=[C:4]([N:27]2[CH2:28][CH2:29][CH:24]([S:21]([CH3:20])(=[O:23])=[O:22])[CH2:25][CH2:26]2)[CH:3]=1

Participants

7

Reactant 4

HCID 174Ethylene Glycol2×HCID 8471TriethylamineHCID 126286025,7-Dichlorothieno[3,2-b]pyridineHCID 230616984-Methanesulfonylpiperidine hydrochloride

Product 1

HCID 57970080HCID 57970080, compoundYield 13%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
120 °C

Procedure

A mixture of 5,7-dichlorothieno[3,2-b]pyridine (0.52 g), triethylamine (0.90 mL), 4-(methylsulfonyl)piperidine mono hydrochloride (0.62 g), and ethylene glycol (1.1 mL) was stirred at 120° C. for 6 h. Ethylene glycol (4.0 mL) and 1,4-dioxane (4.0 mL) were added, and the mixture was further stirred at room temperature for 16 h. The reaction mixture was diluted with ethyl acetate and washed with saturated brine. The organic layer was dried with anhydrous magnesium sulfate, and then silica gel was added to the organic layer. Silica gel and the desiccant were removed by filtration, the filtrate was concentrated under reduced pressure, and the resulting solids were washed with a mixture solution of ethyl acetate and diisopropyl ether. The resulting solids were purified by silica gel column chromatography (ethyl acetate/hexane=1:1-1:0) to obtain 5-chloro-7-(4-(methylsulfonyl)piperidin-1-yl)thieno[3,2-b]pyridine (0.11 g). (2) To a mixture of 5-chloro-7-(4-(methylsulfonyl)piperidin-1-yl)thieno[3,2-b]pyridine (0.11 g), Pd2(dba)3 (0.016 g), (±)-BINAP (0.032 g), 1-((S)-3-aminopyrrolidin-1-yl)-2-(4-trifluoromethoxyphenyl)ethanone mono hydrochloride (0.13 g), and 1,4-dioxane (2.2 mL) was added sodium t-butoxide (0.099 g) under nitrogen atmosphere, and the mixture was stirred at room temperature for 20 h. The mixture was further stirred at 70° C. for 2 h and 30 min. The reaction mixture was diluted with ethyl acetate and water, and then the organic layer was washed with water. The organic layer was dried with anhydrous magnesium sulfate, then the desiccant was removed by filtration, the filtrate was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (NH silica gel, ethyl acetate/hexane=2:1−ethyl acetate/methanol=10:1, and silica gel, chloroform/methanol=50:1-10:1) to obtain colorless amorphous (S)-1-(3-(7-(4-methylsulfonylpiperidin-1-yl)thieno[3,2-b]pyridin-5-ylamino)pyrrolidin-1-yl)-2-(4-trifluoromethoxyphenyl)ethanone (0.074 g).

Workup

  1. stirringthe mixture was further stirred at room temperature for 16 h
  2. washwashed with saturated brine
  3. dry with materialThe organic layer was dried with anhydrous magnesium sulfate
  4. additionsilica gel was added to the organic layer
  5. customSilica gel and the desiccant were removed by filtration
  6. concentrationthe filtrate was concentrated under reduced pressure
  7. washthe resulting solids were washed with a mixture solution of ethyl acetate and diisopropyl ether
  8. customThe resulting solids were purified by silica gel column chromatography (ethyl acetate/hexane=1:1-1:0)

Sources & evidence

ORD record
ord-63bfb2eef4a54d9abe5c3b7f387e3abc
Source dataset
uspto-grants-2011_10
Patent number
US08044068B2

Reaction notes

Loading…