Cesium carbonate → [7-(6-Methoxy-3-trifluoromethyl-pyridin-2-yl)-[1,8]naphthyridin-4-yl]-(5-trifluoromethyl-pyridin-2-yl)-amine

HRID 545079Notes

Reaction equation

HRID 545079 reaction equation
Cl[C:2]1[CH:11]=[CH:10][N:9]=[C:8]2[C:3]=1[CH:4]=[CH:5][C:6]([C:12]1[C:17]([C:18]([F:21])([F:20])[F:19])=[CH:16][CH:15]=[C:14]([O:22][CH3:23])[N:13]=1)=[N:7]2.C(=O)([O-])[O-].[Cs+].[Cs+].[NH2:30][C:31]1[CH:36]=[CH:35][C:34]([C:37]([F:40])([F:39])[F:38])=[CH:33][N:32]=1.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O>[CH3:23][O:22][C:14]1[N:13]=[C:12]([C:6]2[N:7]=[C:8]3[C:3]([C:2]([NH:30][C:31]4[CH:36]=[CH:35][C:34]([C:37]([F:39])([F:38])[F:40])=[CH:33][N:32]=4)=[CH:11][CH:10]=[N:9]3)=[CH:4][CH:5]=2)[C:17]([C:18]([F:21])([F:20])[F:19])=[CH:16][CH:15]=1

Participants

8

Reactant 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 7358622-Amino-5-(trifluoromethyl)pyridineHCID 586455165-Chloro-2-(6-methoxy-3-trifluoromethyl-pyridin-2-yl)-[1,8]naphthyridine

Product 1

HCID 58645536[7-(6-Methoxy-3-trifluoromethyl-pyridin-2-yl)-[1,8]naphthyridin-4-yl]-(5-trifluoromethyl-pyridin-2-yl)-amine

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

To a de-gassed mixture of 5-chloro-2-(6-methoxy-3-trifluoromethyl-pyridin-2-yl)-[1,8]naphthyridine (68 mg, 0.2 mmol), cesium carbonate (98 mg, 0.3 mmol), 2-amino-5-trifluoromethylpyridine (37 mg, 0.22 mmol) in dioxane (5 mL) under nitrogen, add Pd2 dba3 (12 mg) and xantphos (8 mg). Stir the mixture at 100° C. for 14 hours, cool, add water (20 mL) and extract with EtOAc. Dry the combined extracts over Na2SO4, concentrate under vacuum. Purify by chromatography eluting with DCM/MeOH/ammonium hydroxide mixture to give the title compound. 1H NMR δ (CDCl3) 9.01 (1H, brs), 8.59-8.62 (2H, m), 7.98-8.01 (2H, m), 7.91-7.84 (2H, m), 7.23-7.26 (2H, m), 6.90 (1H, d), 3.99 (3H, s). The IC50 determined as described in Example 6 is less than 1 micromolar.

Workup

  1. temperaturecool
  2. extractionextract with EtOAc
  3. dry with materialDry the combined extracts over Na2SO4
  4. concentrationconcentrate under vacuum
  5. customPurify by chromatography
  6. washeluting with DCM/MeOH/ammonium hydroxide mixture

Sources & evidence

ORD record
ord-2bbf003fefc14dfdac00c958b806b7eb
Source dataset
uspto-grants-2011_05
Patent number
US07935702B2

Reaction notes

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