1,4-Dioxane hydrochloride → (R)-1-(naphthalen-1-yl)ethyl-[(S)-1-(6-phenylpyrimidin-4-yl)pyrrolidin-3-yl]amine dihydrochloride

HRID 1622179Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1622179
[C:1]1([C@H:11]([NH:13][C@H:14]2[CH2:18][CH2:17][N:16]([C:19]3[CH:24]=[C:23]([C:25]4[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=4)[N:22]=[CH:21][N:20]=3)[CH2:15]2)[CH3:12])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][CH:2]=1.[ClH:31].O1CCOCC1>>[ClH:31].[ClH:31].[C:1]1([C@H:11]([NH:13][C@H:14]2[CH2:18][CH2:17][N:16]([C:19]3[CH:24]=[C:23]([C:25]4[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=4)[N:22]=[CH:21][N:20]=3)[CH2:15]2)[CH3:12])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][CH:2]=1

Komponenten

3

Edukt 2

HCID 204431481,4-Dioxane hydrochlorideHCID 58973510(R)-1-(naphthalen-1-yl)ethyl-[(S)-1-(6-phenylpyrimidin-4-yl)pyrrolidin-3-yl]amine

Produkt 1

HCID 67408492(R)-1-(naphthalen-1-yl)ethyl-[(S)-1-(6-phenylpyrimidin-4-yl)pyrrolidin-3-yl]amine dihydrochloride

Versuchsvorschrift

In the same manner as in the above-mentioned Example 2.016, 1-[(S)-(6-chloropyrimidin-4-yl)pyrrolidin-3-yl]-(R)-1-(naphthalen-1-yl)ethylamine (a free form of the compound of Example 2.012 in the following Table) was obtained. (2) In 2 ml of toluene were suspended 100 mg of 1-[(S)-(6-chloropyrimidin-4-yl)pyrrolidin-3-yl]-(R)-1-(naphthalen-1-yl)ethylamine, 52 mg of phenyl boronic acid and 78 mg of potassium carbonate, and a nitrogen gas was ventilated for 5 minutes. After adding 32 mg of tetrakistriphenylphosphine palladium to the mixture, the reaction mixture was stirred under nitrogen flow at 100° C. overnight. After standing to cool to room temperature, ethyl acetate and a saturated aqueous sodium bicarbonate solution were added to the reaction mixture, and the liquids were separated. The organic layer was dried, the solvent was evaporated and the obtained residue was purified by silica gel column chromatography (hexane-ethyl acetate) to obtain 46 mg of (R)-1-(naphthalen-1-yl)ethyl-[(S)-1-(6-phenylpyrimidin-4-yl)pyrrolidin-3-yl]amine (3) In 1 ml of tetrahydrofuran was dissolved 46 mg of (R)-1-(naphthalen-1-yl)ethyl-[(S)-1-(6-phenylpyrimidin-4-yl)pyrrolidin-3-yl]amine, 0.2 ml of a solution of 4M hydrochloric acid-dioxane was added, and the mixture was allowed to stand at room temperature. The precipitated solids were collected by filtration, washed with ether, and dried to obtain 41 mg of (R)-1-(naphthalen-1-yl)ethyl-[(S)-1-(6-phenylpyrimidin-4-yl)pyrrolidin-3-yl]amine dihydrochloride (Example 3.018 in the following Table A3).

Aufarbeitung

  1. additionwas added
  2. customto stand at room temperature
  3. filtrationThe precipitated solids were collected by filtration
  4. washwashed with ether
  5. customdried

Quellen und Nachweise

ORD-Eintrag
ord-33bbdebb923440cd9d5329a702bc8cc3
Quelldatensatz
uspto-grants-2014_07
Patentnummer
US08778628B2

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