1-Phenethylamine, (-)- → (S)-[4-(3-Chloro-indazol-1-yl)-pyridin-2-yl]-(1-phenyl-ethyl)-amine

HRID 729527Notes

Reaction equation

[Cl:1][C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[N:4]([C:11]2[CH:16]=[CH:15][N:14]=[C:13](Cl)[CH:12]=2)[N:3]=1.C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[CH3:64][C@H:65]([NH2:72])[C:66]1[CH:71]=[CH:70][CH:69]=[CH:68][CH:67]=1.CC(C)([O-])C.[Na+]>C1(C)C=CC=CC=1.C(Cl)Cl.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[Cl:1][C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[N:4]([C:11]2[CH:16]=[CH:15][N:14]=[C:13]([NH:72][C@H:65]([C:66]3[CH:71]=[CH:70][CH:69]=[CH:68][CH:67]=3)[CH3:64])[CH:12]=2)[N:3]=1

Participants

Conditions

Temperature: 70 °C

Procedure

To a solution of 3-chloro-1-(2-chloro-pyridin-4-yl)-1H-indazole (0.29 g, 1.1 mmol) in toluene (6 mL) under nitrogen were added palladium acetate (0.025 g, 0.11 mmol), rac-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (0.069 g, 0.1 mmol), and (S)-(−)-α-methylbenzylamine (0.18 mL, 1.38 mmol), followed by sodium t-butoxide (0.3 g, 3.1 mmol). The resulting mixture was heated at 70° C. for 1 h, during which TLC and HPLC indicated completion of reaction. After cooling to room temperature, the reaction was diluted with methylene chloride and washed with saturated sodium bicarbonate and brine and dried over MgSO4. Flash chromatography of the crude product mixture with 25:10:65, 35:10:55, and 50:10:40 EtOAc-CH2Cl2-hexane gave the title compound as a tan colored solid. MS (ES+): 349.3 [M+H]+, 347.1 [M−H]−.

Workup

customcompletion of reaction
temperatureAfter cooling to room temperature
washwashed with saturated sodium bicarbonate and brine
dry with materialdried over MgSO4

Sources & evidence

ORD record: ord-dbb28ce2443f43978b1f7bf7b806ec71
Source dataset: uspto-grants-2009_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07582631B2

Reaction notes

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