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

HRID 2264904Notes

Reaction equation

HRID 2264904 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[NH:14][C:13]2[CH:12]=[CH:11][N:10]=[CH:9][C:8]=2[C:7]=1[NH2:15])=[O:5])[CH3:2].[F:16][C:17]1[CH:22]=[C:21]([Si:23]([CH3:26])([CH3:25])[CH3:24])[CH:20]=[CH:19][C:18]=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.CCOC(C)=O.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[CH:12]=[CH:11][N:10]=[CH:9][C:8]=2[C:7]=1[NH:15][C:18]1[CH:19]=[CH:20][C:21]([Si:23]([CH3:25])([CH3:24])[CH3:26])=[CH:22][C:17]=1[F:16])=[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 23218185ethyl 3-amino-1H-pyrrolo[3,2-c]pyridine-2-carboxylateHCID 59596436Trifluoromethanesulfonic acid 2-fluoro-4-trimethylsilanyl-phenyl ester

Product 1

HCID 595966623-(2-Fluoro-4-trimethylsilanyl-phenylamino)-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid ethyl esterYield 42%

Reagents, catalysts & solvents 3

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

Procedure

A degassed solution of 3-amino-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid ethyl ester (200 mg, 0.98 mmol), trifluoro-methanesulfonic acid 2-fluoro-4-trimethylsilanyl-phenyl ester (324 mg, 1.02 mmol), Pd2dba3 (44 mg, 0.048 mmol), Xantphos (56 mg, 0.098 mmol) and Cs2CO3 (636 mg, 1.95 mmol) in toluene (6 ml) was subjected to microwave irradiation at 150° C. for 20 minutes. The reaction mixture was cooled to ambient temperature then diluted with EtOAc (100 ml). The resultant solution was washed with water (60 ml), dried (Na2SO4) and concentrated in vacuo to give a black oil. The oil was purified by flash chromatography (Si-PPC, cyclohexane:EtOAc, gradient 90:10 to 20:80) to provide the title compound as a brown solid (152 mg, 42%). LCMS (method B): RT=2.65 min, M+H+=372.

Workup

  1. customirradiation at 150° C. for 20 minutes
  2. washThe resultant solution was washed with water (60 ml)
  3. dry with materialdried (Na2SO4)
  4. concentrationconcentrated in vacuo
  5. customto give a black oil
  6. customThe oil was purified by flash chromatography (Si-PPC, cyclohexane:EtOAc, gradient 90:10 to 20:80)

Sources & evidence

ORD record
ord-42e27945d5ab446989cbfd9d19de7a00
Source dataset
uspto-grants-2010_12
Patent number
US07855216B2

Reaction notes

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