1-Butanol → HCID 57970075, compound

HRID 1666608Notes

Reaction equation

HRID 1666608 reaction equation
Cl[C:2]1[CH:11]=[C:10]([CH3:12])[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[N:3]=1.Cl.[NH2:14][C@H:15]1[CH2:19][CH2:18][N:17]([C:20](=[O:33])[CH2:21][C:22]2[CH:27]=[CH:26][C:25]([O:28][C:29]([F:32])([F:31])[F:30])=[CH:24][CH:23]=2)[CH2:16]1.C(N(CC)C(C)C)(C)C.C(O)CCC>C(Cl)(Cl)Cl.C(=O)([O-])O.[Na+]>[CH3:12][C:10]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[N:3]=[C:2]([NH:14][C@H:15]2[CH2:19][CH2:18][N:17]([C:20](=[O:33])[CH2:21][C:22]3[CH:23]=[CH:24][C:25]([O:28][C:29]([F:30])([F:31])[F:32])=[CH:26][CH:27]=3)[CH2:16]2)[CH:11]=1

Participants

7

Reactant 4

HCID 2631-ButanolHCID 694492-Chloro-4-methylquinolineHCID 81531DiisopropylethylamineHCID 86636479(S)-1-(3-aminopyrrolidin-1-yl)-2-(4-trifluoromethoxyphenyl)ethanone mono hydrochloride

Product 1

HCID 57970075HCID 57970075, compoundYield 33.1%

Reagents, catalysts & solvents 2

HCID 6212ChloroformSolventHCID 516892Sodium BicarbonateSolvent

Conditions

Temperature
140 °C

Procedure

A mixture of 2-chloro-4-methylquinoline (0.30 g), 1-((S)-3-aminopyrrolidin-1-yl)-2-(4-trifluoromethoxyphenyl)ethanone mono hydrochloride (0.60 g), N,N-diisopropylethylamine (0.74 mL), and n-butanol (1.5 mL) was heated at 140° C. in a sealed tube for 23 h. The reaction mixture was diluted with chloroform and saturated aqueous sodium hydrogencarbonate, and then the aqueous layer was extracted with chloroform. The organic layer was dried with anhydrous sodium sulfate, 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, hexane/ethyl acetate=1:1) to obtain 1-((S)-3-(4-methylquinolin-2-ylamino)pyrrolidin-1-yl)-2-(4-trifluoromethoxyphenyl)ethanone (0.24 g). (2) 1-((S)-3-(4-Methylquinolin-2-ylamino)pyrrolidin-1-yl)-2-(4-trifluoromethoxyphenyl)ethanone (0.24 g) was dissolved in ethyl acetate (2.5 mL), followed by addition of a solution (0.28 mL) of 4 M HCl in ethyl acetate, the mixture was stirred at room temperature for 2 h, concentrated under reduced pressure, and then solidified with diethyl ether to obtain the title compound (0.24 g).

Workup

  1. extractionthe aqueous layer was extracted with chloroform
  2. dry with materialThe organic layer was dried with anhydrous sodium sulfate
  3. customthe desiccant was removed by filtration
  4. concentrationthe filtrate was concentrated under reduced pressure
  5. customthe residue was purified by silica gel column chromatography (NH silica gel, hexane/ethyl acetate=1:1)

Sources & evidence

ORD record
ord-2125a56baf0c4f0fac763b8541f7f00f
Source dataset
uspto-grants-2011_10
Patent number
US08044068B2

Reaction notes

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