Cesium carbonate → N-[5-(1H-Pyrrolo[2,3-b]pyridin-3-ylmethyl)-pyridin-2-yl]-4-trifluoromethyl-benzamide

HRID 1754658Notes

Reaction equation

HRID 1754658 reaction equation
Br[C:2]1[N:7]=[CH:6][C:5]([CH2:8][C:9]2[C:17]3[C:12](=[N:13][CH:14]=[CH:15][CH:16]=3)[N:11]([Si](C(C)C)(C(C)C)C(C)C)[CH:10]=2)=[CH:4][CH:3]=1.[F:28][C:29]([F:40])([F:39])[C:30]1[CH:38]=[CH:37][C:33]([C:34]([NH2:36])=[O:35])=[CH:32][CH:31]=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.C(=O)([O-])[O-].[Cs+].[Cs+]>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>[NH:11]1[C:12]2=[N:13][CH:14]=[CH:15][CH:16]=[C:17]2[C:9]([CH2:8][C:5]2[CH:4]=[CH:3][C:2]([NH:36][C:34](=[O:35])[C:33]3[CH:37]=[CH:38][C:30]([C:29]([F:39])([F:40])[F:28])=[CH:31][CH:32]=3)=[N:7][CH:6]=2)=[CH:10]1

Participants

8

Reactant 4

HCID 10796Cesium carbonateHCID 746844-(Trifluoromethyl)benzamideHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 584421163-(6-Bromo-pyridin-3-ylmethyl)-1-triisopropylsilanyl-1H-pyrrolo[2,3-b]pyridine

Product 1

HCID 59593310N-[5-(1H-Pyrrolo[2,3-b]pyridin-3-ylmethyl)-pyridin-2-yl]-4-trifluoromethyl-benzamide

Reagents, catalysts & solvents 3

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

Conditions

Temperature
120 °C

Procedure

To 3-(6-Bromo-pyridin-3-ylmethyl)-1H-pyrrolo[2,3-b]pyridine (6a, 50.0 mg, 0.000174 mol, prepared as described in Example 2) in 1,4-dioxane (4.0 mL) were added 4-trifluoromethyl-benzamide (51, 70.0 mg, 0.37 mmol), Xanthphos (15.0 mg, 0.026 mmol), cesium carbonate (130.0 mg, 0.40 mmol) and Tris(dibenzylideneacetone)-dipalladium(0) (25.0 mg, 0.024 mmol) under an atmosphere of nitrogen. The reaction was heated to 120° C. for 10 minutes in a CEM Discover microwave instrument. The reaction was poured into water and extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated and purified by silica gel column chromatography eluting with 50% ethyl acetate in hexane to give a white solid (P-0072, 4.7 mg, 6.8%). MS (ESI) [M+H+]+=397.2.

Workup

  1. extractionextracted with ethyl acetate
  2. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  3. filtrationfiltered
  4. concentrationThe filtrate was concentrated
  5. custompurified by silica gel column chromatography
  6. washeluting with 50% ethyl acetate in hexane
  7. customto give a white solid (P-0072, 4.7 mg, 6.8%)

Sources & evidence

ORD record
ord-8396be2775d54ab7bf362bb7619cc3e5
Source dataset
uspto-grants-2015_10
Patent number
US09169250B2

Reaction notes

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