Cesium carbonate → HCID 86605108, compound

HRID 545099Notes

Reaction equation

HRID 545099 reaction equation
[CH2:1]([O:3][C:4]1[N:9]=[N:8][C:7]([C:10]2[N:15]=[C:14]3[N:16]=[CH:17][CH:18]=[C:19]([NH2:20])[C:13]3=NC=2)=[C:6]([C:21]([F:24])([F:23])[F:22])[CH:5]=1)[CH3:2].Cl[C:26]1[CH:31]=[CH:30][C:29]([C:32]([F:35])([F:34])[F:33])=[CH:28][N:27]=1.C([O-])([O-])=O.[Cs+].[Cs+].[CH3:42][C:43]1(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.CC(C)=O.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]>[CH2:1]([O:3][C:4]1[N:9]=[N:8][C:7]([C:10]2[N:15]=[C:14]3[C:13]([C:19]([NH:20][C:26]4[CH:31]=[CH:30][C:29]([C:32]([F:35])([F:34])[F:33])=[CH:28][N:27]=4)=[CH:18][CH:17]=[N:16]3)=[CH:43][CH:42]=2)=[C:6]([C:21]([F:24])([F:22])[F:23])[CH:5]=1)[CH3:2]

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 58645511HCID 58645511, compound

Product 1

HCID 86605108HCID 86605108, compound

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 180AcetoneSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
110 °C

Procedure

In a sealed tube, add 3-[6-ethoxy-4-(trifluoromethyl)pyridazin-3-yl]pyrido[2,3-b]pyrazin-8-amine (290 mg, 0.862 mmol), 2-chloro-5-trifluoromethyl-pyridine (172 mg, 0.948 mmol), and Cs2CO3 (842 mg, 2.58 mmol) in dry dioxane (8 mL). Bubble argon through the solution for 5 minutes. Add Pd2 dba3 (79 mg, 0.0862 mmol) and xantphos (50 mg, 0.0862 mmol). Bubble argon through the solution for an additional 5 minutes. Seal the tube and heat the mixture at 110° C. overnight. Cool the mixture to room temperature and dilute with acetone (10 mL). Filter the mixture through Celite, washing with acetone. Evaporate the solvent under reduced pressure. Purify the crude residue by chromatography on silica gel eluting with Hexane/EtOAc (3/1) to yield the title compound. 1H NMR (CDCl3) δ 9.52 (s, 1H), 9.43 (br s, 1H), 9.12 (d, 1H), 8.92 (d, 1H), 8.73 (br s, 1H), 7.91 (dd, 1H), 7.48 (s, 1H), 7.15 (d, 1H), 4.78 (q, 2H), 1.55 (t, 3H). LC/MS (MH+) 482.10. The IC50 determined as described in Example 6 is less than 1 micromolar.

Workup

  1. waitBubble argon through the solution for an additional 5 minutes
  2. customSeal the tube
  3. temperatureCool the mixture to room temperature
  4. filtrationFilter the mixture through Celite
  5. washwashing with acetone
  6. customEvaporate the solvent under reduced pressure
  7. customPurify the crude residue by chromatography on silica gel eluting with Hexane/EtOAc (3/1)

Sources & evidence

ORD record
ord-7d9496cadc6042b492be7b50a26c06b4
Source dataset
uspto-grants-2011_05
Patent number
US07935702B2

Reaction notes

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