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

HRID 2264932Notes

Reaction equation

HRID 2264932 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[N:14]([CH3:15])[C:13]2[C:12]([F:16])=[CH:11][N:10]=[CH:9][C:8]=2[C:7]=1[NH2:17])=[O:5])[CH3:2].[F:18][C:19]1[CH:24]=[C:23]([Si:25]([CH3:28])([CH3:27])[CH3:26])[CH:22]=[CH:21][C:20]=1OS(C(F)(F)F)(=O)=O.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].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>[CH2:1]([O:3][C:4]([C:6]1[N:14]([CH3:15])[C:13]2[C:12]([F:16])=[CH:11][N:10]=[CH:9][C:8]=2[C:7]=1[NH:17][C:20]1[CH:21]=[CH:22][C:23]([Si:25]([CH3:27])([CH3:26])[CH3:28])=[CH:24][C:19]=1[F:18])=[O:5])[CH3:2]

Participants

7

Reactant 3

HCID 10796Cesium carbonateHCID 59596436Trifluoromethanesulfonic acid 2-fluoro-4-trimethylsilanyl-phenyl esterHCID 595966593-Amino-7-fluoro-1-methyl-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid ethyl ester

Product 1

HCID 595965847-Fluoro-3-(2-fluoro-4-trimethylsilanyl-phenylamino)-1-methyl-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid ethyl esterYield 138.3%

Reagents, catalysts & solvents 3

HCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Procedure

A degassed solution of 3-amino-7-fluoro-1-methyl-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid ethyl ester (900 mg, 3.8 mmol), trifluoro-methanesulfonic acid 2-fluoro-4-trimethylsilanyl-phenyl ester (1.44 mg, 4.56 mmol), Pd2dba3 (174 mg, 0.19 mmol), Xantphos (220 mg, 0.38 mmol) and Cs2CO3 (2.48 g, 7.6 mmol) in toluene (10 ml) was heated at 150° C. for 20 minutes using microwave irradiation. The reaction mixture was cooled to ambient temperature then filtered through a pad of Celite® washing with ethyl acetate. The filtrate was concentrated in vacuo and the resultant residue subjected to flash chromatography (Si-PPC, gradient 0-30% ethyl acetate in cyclohexane) to provide the title compound as a yellow/orange solid (2.12 g, 69%). LCMS (method B): RT=4.15 min, M+H+ 404.

Workup

  1. custommicrowave irradiation
  2. filtrationthen filtered through a pad of Celite®
  3. washwashing with ethyl acetate
  4. concentrationThe filtrate was concentrated in vacuo

Sources & evidence

ORD record
ord-6b8f013cc4d4405682ca28c3de3d72bc
Source dataset
uspto-grants-2010_12
Patent number
US07855216B2

Reaction notes

Loading…