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

HRID 1811628Notes

Reaction equation

HRID 1811628 reaction equation
[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>O1CCCC1>[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

Participants

4

Reactant 2

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

Product 1

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

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

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).

Workup

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

Sources & evidence

ORD record
ord-8c9030586aba458d8692c31cfadf2229
Source dataset
uspto-grants-2013_01
Patent number
US08362274B2

Reaction notes

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