Toluene → (R)-1-(naphthalen-1-yl)ethyl-[(S)-1-(6-phenylpyrimidin-4-yl)pyrrolidin-3-yl]amine

HRID 1622178Notes

Reaction equation

HRID 1622178 reaction equation
[C:1]([C:4]1[CH:9]=[CH:8][C:7]([N:10]2[CH2:14][CH2:13][C@H:12]([NH:15][C@@H:16]([C:18]3C4C(=CC=CC=4)C=CC=3)C)[CH2:11]2)=[CH:6][CH:5]=1)(=O)[CH3:2].ClC1N=C[N:32]=[C:31]([N:35]2CC[C@H]([C@@](N)(C3C4C(=CC=CC=4)C=CC=3)C)C2)C=1.[C:53]1(B(O)O)[CH:58]=[CH:57][CH:56]=[CH:55][CH:54]=1.C(=O)([O-])[O-].[K+].[K+].[C:68](=O)(O)[O-].[Na+].[C:73]1(C)C=C[CH:76]=[CH:75][CH:74]=1>C(OCC)(=O)C>[C:53]1([C@H:16]([NH:15][C@H:12]2[CH2:13][CH2:14][N:10]([C:7]3[CH:8]=[C:9]([C:4]4[CH:1]=[CH:2][CH:68]=[CH:6][CH:5]=4)[N:35]=[CH:31][N:32]=3)[CH2:11]2)[CH3:18])[C:58]2[C:57](=[CH:73][CH:74]=[CH:75][CH:76]=2)[CH:56]=[CH:55][CH:54]=1

Participants

8

Reactant 6

HCID 1140TolueneHCID 11430Potassium CarbonateHCID 66827Phenylboronic AcidHCID 516892Sodium BicarbonateHCID 58973483(S)-1-(4-acetylphenyl)pyrrolidin-3-yl-[(R)-1-(naphthalen-1-yl)ethyl]amineHCID 873878241-[(s)-(6-Chloropyrimidin-4-yl)pyrrolidin-3-yl]-(r)-1-(naphthalen-1-yl)ethylamine

Product 1

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

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

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. temperatureto cool to room temperature
  2. customthe liquids were separated
  3. customThe organic layer was dried
  4. customthe solvent was evaporated
  5. customthe obtained residue was purified by silica gel column chromatography (hexane-ethyl acetate)

Sources & evidence

ORD record
ord-4269fd657d3346d99ab9a4d68fcd2964
Source dataset
uspto-grants-2014_07
Patent number
US08778628B2

Reaction notes

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