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

HRID 2264898Notes

Reaction equation

HRID 2264898 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[N:14]([CH3:15])[C:13]2[CH:12]=[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]>[CH2:1]([O:3][C:4]([C:6]1[N:14]([CH3:15])[C:13]2[CH:12]=[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

7

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 59596525HCID 59596525, compound

Product 1

HCID 595964973-(2-Fluoro-4-trimethylsilanyl-phenylamino)-1-methyl-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid ethyl esterYield 85.1%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Procedure

3-Amino-1-methyl-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid ethyl ester (25 g, 114 mmol), trifluoro-methanesulfonic acid 2-fluoro-4-trimethylsilanyl-phenyl ester (47.0 g, 149 mmol), Pd2(dba)3 (5.0 g, 5.5 mmol), Xantphos (6.5 g, 11.3 mmol) and cesium carbonate (74.5 g, 228 mmol) were suspended in toluene (500 mL) and the flask evacuated and purged with argon. The reaction mixture was heated at reflux for 18 hours. The mixture was cooled and filtered through Celite® washing through with toluene. The filtrate was evaporated in vacuo and the residue subjected to flash chromatography (SiO2, gradient 0-10% MeOH in DCM) to give the title compound (37.4 g, 85%) as a yellow solid. 1H NMR (CDCl3) 8.79 (1H, d, J=1.1 Hz), 8.39 (1H, d, J=6.1 Hz), 7.60 (1H, s, br), 7.25 (0.5H, s), 7.22 (1H, s), 7.21 (0.5H, d, J=1.0 Hz), 7.14-7.10, (2H, m), 4.42 (2H, q, J=7.0 Hz), 3.97 (3H, s), 1.44 (3H, t, J=7.0 Hz), 0.26 (9H, s).

Workup

  1. customthe flask evacuated
  2. custompurged with argon
  3. temperatureThe reaction mixture was heated
  4. temperatureat reflux for 18 hours
  5. temperatureThe mixture was cooled
  6. filtrationfiltered through Celite®
  7. washwashing through with toluene
  8. customThe filtrate was evaporated in vacuo

Sources & evidence

ORD record
ord-9c5078264cc74a2390fd5829aa271a38
Source dataset
uspto-grants-2010_12
Patent number
US07855216B2

Reaction notes

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