Cesium carbonate → HCID 46911175, compound

HRID 545076Notes

Reaction equation

HRID 545076 reaction equation
[NH2:1][C:2]1[C:11]2[C:6](=[N:7][C:8]([C:12]3[C:20]([C:21]([F:24])([F:23])[F:22])=[CH:19][C:15]([C:16]([NH2:18])=[O:17])=[CH:14][N:13]=3)=[CH:9][N:10]=2)[N:5]=[CH:4][CH:3]=1.C(=O)([O-])[O-].[Cs+].[Cs+].Cl[C:32]1[CH:37]=[CH:36][C:35]([C:38]([F:41])([F:40])[F:39])=[CH:34][N:33]=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>[F:22][C:21]([F:24])([F:23])[C:20]1[C:12]([C:8]2[N:7]=[C:6]3[N:5]=[CH:4][CH:3]=[C:2]([NH:1][C:32]4[CH:37]=[CH:36][C:35]([C:38]([F:41])([F:40])[F:39])=[CH:34][N:33]=4)[C:11]3=[N:10][CH:9]=2)=[N:13][CH:14]=[C:15]([CH:19]=1)[C:16]([NH2:18])=[O:17]

Participants

8

Reactant 4

HCID 10796Cesium carbonateHCID 923422-Chloro-5-(trifluoromethyl)pyridineHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 58645644HCID 58645644, compound

Product 1

HCID 46911175HCID 46911175, compound

Reagents, catalysts & solvents 3

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

Conditions

Temperature
100 °C

Procedure

To a de-gassed mixture of 6-(8-amino-pyrido[2,3-b]pyrazin-3-yl)-5-trifluoromethyl-nicotinamide (51 mg, 0.15 mmol), cesium carbonate (98 mg, 0.3 mmol), 2-chloro-5-trifluoromethyl pyridine (27 mg, 0.15 mmol) in dioxane (5 mL) under nitrogen, add Pd2 dba3 (9 mg) and xantphos (7 mg). Stir the mixture at 100° C. for 3 hours, cool, add water (10 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. MS 480.15 (M+1). 1H NMR δ (CDCl3) 9.82 (1H, s), 9.30-9.32 (2H, m), 8.98 (1H, d), 8.71 (1H, d), 8.62 (1H, s), 8.49 (1H, d), 7.98 (1H, dd), 7.50 (1H, d). 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-17b0ace4d07e4754a3731e01a3b169ac
Source dataset
uspto-grants-2011_05
Patent number
US07935702B2

Reaction notes

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