1-Pyrrolidinamine → HCID 57970106, compound

HRID 1666632Notes

Reaction equation

HRID 1666632 reaction equation
NN1CCCC1.Cl[C:8]1[N:13]=[C:12]2[CH:14]=[CH:15][S:16][C:11]2=[C:10]([N:17]2[CH2:22][CH2:21][CH:20]([S:23]([CH3:26])(=[O:25])=[O:24])[CH2:19][CH2:18]2)[CH:9]=1.Cl.[NH2:28][C@H:29]1[CH2:33][CH2:32][N:31]([C:34](=[O:47])[CH2:35][C:36]2[CH:41]=[CH:40][C:39]([O:42][C:43]([F:46])([F:45])[F:44])=[CH:38][CH:37]=2)[CH2:30]1.CC(C)([O-])C.[Na+]>C(OCC)(=O)C.O.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O1CCOCC1>[CH3:26][S:23]([CH:20]1[CH2:21][CH2:22][N:17]([C:10]2[CH:9]=[C:8]([NH:28][C@H:29]3[CH2:33][CH2:32][N:31]([C:34](=[O:47])[CH2:35][C:36]4[CH:37]=[CH:38][C:39]([O:42][C:43]([F:44])([F:45])[F:46])=[CH:40][CH:41]=4)[CH2:30]3)[N:13]=[C:12]3[CH:14]=[CH:15][S:16][C:11]=23)[CH2:18][CH2:19]1)(=[O:25])=[O:24]

Participants

9

Reactant 4

HCID 279461-PyrrolidinamineHCID 23676156Sodium t-butoxideHCID 57970080HCID 57970080, compoundHCID 86636479(S)-1-(3-aminopyrrolidin-1-yl)-2-(4-trifluoromethoxyphenyl)ethanone mono hydrochloride

Product 1

HCID 57970106HCID 57970106, compoundYield 38.2%

Reagents, catalysts & solvents 4

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

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 70° C. for 2 h and 30 min
  2. washthe organic layer was washed with water
  3. dry with materialThe organic layer was dried with anhydrous magnesium sulfate
  4. customthe desiccant was removed by filtration
  5. concentrationthe filtrate was concentrated under reduced pressure
  6. customthe 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)

Sources & evidence

ORD record
ord-18c1a8fdac0c42b68d80adc7b69ae146
Source dataset
uspto-grants-2011_10
Patent number
US08044068B2

Reaction notes

Loading…