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

HRID 1366791Notes

Reaction equation

HRID 1366791 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[S: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.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].C(OCC)C.CCCCC>[CH2:1]([O:3][C:4]([C:6]1[S: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

9

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 597039033-Amino-7-fluoro-thieno[3,2-c]pyridine-2-carboxylic acid ethyl ester

Product 1

HCID 597038867-Fluoro-3-(2-fluoro-4-trimethylsilanyl-phenylamino)-thieno[3,2-c]pyridine-2-carboxylic acid ethyl esterYield 64%

Reagents, catalysts & solvents 4

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolventHCID 3283Diethyl EtherSolventHCID 8003PentaneSolvent

Procedure

A mixture of 3-amino-7-fluoro-thieno[3,2-c]pyridine-2-carboxylic acid ethyl ester (360 mg, 1.5 mmol), trifluoro-methanesulfonic acid 2-fluoro-4-trimethylsilanyl-phenyl ester (411 mg, 1.3 mmol), Pd2 dba3 (69 mg, 0.075 mmol), Xantphos (86 mg, 0.15 mmol) and Cs2CO3 (685 mg, 2.1 mmol) in toluene (6 ml) was subjected to microwave irradiation at 160° C. for 20 minutes. The reaction mixture was filtered through a pad of Celite®. The filtrate was concentrated under reduced pressure to give a residue which was subjected to flash chromatography (Si-SPE, pentane:diethyl ether, gradient 100:0 to 90:10) to give the title compound as a yellow solid (338 mg, 55%). LCMS (method B): RT=5.20 min, M+H+=407.

Workup

  1. customirradiation at 160° C. for 20 minutes
  2. filtrationThe reaction mixture was filtered through a pad of Celite®
  3. concentrationThe filtrate was concentrated under reduced pressure
  4. customto give a residue which

Sources & evidence

ORD record
ord-a529cd0f96024c53a6c606ab994380f8
Source dataset
uspto-grants-2011_02
Patent number
US07893085B2

Reaction notes

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