Cesium carbonate → 7-Fluoro-3-(2-fluoro-4-trimethylsilanyl-phenylamino)-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid ethyl ester

HRID 2264936Notes

Reaction equation

HRID 2264936 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[NH:14][C:13]2[C:12]([F:15])=[CH:11][N:10]=[CH:9][C:8]=2[C:7]=1[NH2:16])=[O:5])[CH3:2].[F:17][C:18]1[CH:23]=[C:22]([Si:24]([CH3:27])([CH3:26])[CH3:25])[CH:21]=[CH:20][C:19]=1OS(C(F)(F)F)(=O)=O.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+]>C1(C)C=CC=CC=1.C(OCC)(=O)C.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]([C:6]1[NH:14][C:13]2[C:12]([F:15])=[CH:11][N:10]=[CH:9][C:8]=2[C:7]=1[NH:16][C:19]1[CH:20]=[CH:21][C:22]([Si:24]([CH3:26])([CH3:25])[CH3:27])=[CH:23][C:18]=1[F:17])=[O:5])[CH3:2]

Participants

8

Reactant 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 59596436Trifluoromethanesulfonic acid 2-fluoro-4-trimethylsilanyl-phenyl esterHCID 595966093-Amino-7-fluoro-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid ethyl ester

Product 1

HCID 595964727-Fluoro-3-(2-fluoro-4-trimethylsilanyl-phenylamino)-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid ethyl esterYield 29%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Procedure

A degassed solution of 3-amino-7-fluoro-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid ethyl ester (1.0 g, 4.48 mmol), trifluoro-methanesulfonic acid 2-fluoro-4-trimethylsilanyl-phenyl ester (1.6 g, 4.93 mmol), Pd2dba3 (205 mg, 0.22 mmol), Xantphos (258 mg, 0.45 mmol) and cesium carbonate (2.0 g, 6.28 mmol) in toluene (20 ml) was subjected to microwave irradiation at 150° C. for 20 minutes. The reaction mixture was cooled to ambient temperature then diluted with ethyl acetate and filtered through a pad of Celite®. The filtrate was concentrated under reduced pressure to give a residue that was purified by flash chromatography (Si-PPC, pentane:diethyl ether, gradient 100:0 to 0:100) to afford the title compound as a yellow solid (505 mg, 29%). LCMS (method B): RT=3.39 min, M+H+=390.

Workup

  1. customirradiation at 150° C. for 20 minutes
  2. filtrationfiltered through a pad of Celite®
  3. concentrationThe filtrate was concentrated under reduced pressure
  4. customto give a residue that
  5. customwas purified by flash chromatography (Si-PPC, pentane:diethyl ether, gradient 100:0 to 0:100)

Sources & evidence

ORD record
ord-cc4e02f7ad87457fbd347e8af781f3d3
Source dataset
uspto-grants-2010_12
Patent number
US07855216B2

Reaction notes

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