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

HRID 2264926Notes

Reaction equation

HRID 2264926 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[NH:14][C:13]2[C:12]([Cl: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.C(=O)([O-])[O-].[Cs+].[Cs+].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>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[NH:14][C:13]2[C:12]([Cl: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

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 59596637ethyl 3-amino-7-chloro-1H-pyrrolo[3,2-c]pyridine-2-carboxylate

Product 1

HCID 595965967-Chloro-3-(2-fluoro-4-trimethylsilanyl-phenylamino)-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid ethyl esterYield 50%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
150 °C

Procedure

To a solution of 3-amino-7-chloro-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid ethyl ester (1.0 g, 4.18 mmol) and trifluoromethanesulfonic acid 2-fluoro-4-trimethylsilanyl-phenyl ester (1.45 g, 4.59 mmol) in toluene (18 ml) was added cesium carbonate (1.90 g, 5.85 mmol) before the mixture was degassed. Pd2dba3 (382 mg, 0.418 mmol) and Xantphos (482 mg, 0.835 mmol) were then added and the vessel was flushed with argon. The resultant reaction mixture was heated at 150° C. under microwave irradiation for 31 min, cooled and filtered through Hyflo washing with ethyl acetate. The filtrate was washed with saturated sodium bicarbonate, the organic layer dried (MgSO4) and concentrated in vacuo. Purification of the resultant residue by flash chromatography (Si-PPC, dichloromethane:ethyl acetate gradient 1:0 to 5:1) afforded the title compound as a pale yellow solid (0.84 g, 50%). LCMS (method B): RT=3.75 min, M+H+=406.

Workup

  1. customwas degassed
  2. customthe vessel was flushed with argon
  3. customThe resultant reaction mixture
  4. temperaturecooled
  5. filtrationfiltered through Hyflo
  6. washwashing with ethyl acetate
  7. washThe filtrate was washed with saturated sodium bicarbonate
  8. dry with materialthe organic layer dried (MgSO4)
  9. concentrationconcentrated in vacuo
  10. customPurification of the resultant residue by flash chromatography (Si-PPC, dichloromethane:ethyl acetate gradient 1:0 to 5:1)

Sources & evidence

ORD record
ord-de0a64fb106c43e184ba32d9fb20687b
Source dataset
uspto-grants-2010_12
Patent number
US07855216B2

Reaction notes

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