Hydrochloric Acid → (1R)-1-{4-[3-phenyl-5-(1H-pyrazol-4-yl)-1,6-naphthyridin-2-yl]phenyl}ethanamine

HRID 1920035Notes

Reaction equation

Cl[C:2]1[N:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[CH:4]=[C:5]([C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)[C:6]([C:12]1[CH:17]=[CH:16][C:15]([CH:18]([NH:20]S(C(C)(C)C)=O)[CH3:19])=[CH:14][CH:13]=1)=[N:7]2.CC1(C)C(C)(C)OB([C:41]2[CH:42]=[N:43][N:44](C(OC(C)(C)C)=O)[CH:45]=2)O1.C(=O)([O-])[O-].[Cs+].[Cs+].Cl>CCOCC.CC(C)([P](C(C)(C)C)([Pd][P](C(C)(C)C)(C(C)(C)C)C(C)(C)C)C(C)(C)C)C.O1CCOCC1.C(O)C.O>[C:27]1([C:5]2[C:6]([C:12]3[CH:17]=[CH:16][C:15]([C@H:18]([NH2:20])[CH3:19])=[CH:14][CH:13]=3)=[N:7][C:8]3[C:3]([CH:4]=2)=[C:2]([C:41]2[CH:42]=[N:43][NH:44][CH:45]=2)[N:11]=[CH:10][CH:9]=3)[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=1

Participants

Conditions

Temperature: 100 °C

Procedure

A solution of N-{1-[4-(5-chloro-3-phenyl-1,6-naphthyridin-2-yl)phenyl]ethyl}-2-methylpropane-2-sulfinamide (2-3, 0.10 g, 0.22 mmol), tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole-1-carboxylate (0.12 g, 0.39 mmol), cesium carbonate (0.21 g, 0.64 mmol) and bis(tri-t-butylphosphine)palladium(0) (0.013 g, 0.025 mmol) in a 7/3/1 mixture of dioxane/ethanol/water (3 mL) was heated to 100° C. in a microwave for 10 minutes. The crude reaction mixture was treated with HCl in ether (3 mL). After 30 minutes, the reaction was concentrated and purified by reverse phase chromatography (5-95% acetonitrile/water/0.1% TFA, Sunfire C18) to give (1R)-1-{4-[3-phenyl-5-(1H-pyrazol-4-yl)-1,6-naphthyridin-2-yl]phenyl}ethanamine (2-4) as a white solid. MS (M+H)+: 428

Workup

customThe crude reaction mixture
concentrationthe reaction was concentrated
custompurified by reverse phase chromatography (5-95% acetonitrile/water/0.1% TFA, Sunfire C18)

Sources & evidence

ORD record: ord-4d36d1c36cb34f788fa08e48356d3620
Source dataset: uspto-grants-2012_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08168652B2

Reaction notes

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