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

HRID 2264908Notes

Reaction equation

HRID 2264908 reaction equation
[CH3:1][O:2][C:3]([C:5]1[N:13]([CH2:14][C:15]2[CH:20]=[CH:19][C:18]([O:21][CH3:22])=[CH:17][CH:16]=2)[C:12]2[CH:11]=[CH:10][N:9]=[CH:8][C:7]=2[C:6]=1[NH2:23])=[O:4].C([O-])([O-])=O.[Cs+].[Cs+].[F:30][C:31]1[CH:36]=[C:35]([Si:37]([CH3:40])([CH3:39])[CH3:38])[CH:34]=[CH:33][C:32]=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>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]>[CH3:1][O:2][C:3]([C:5]1[N:13]([CH2:14][C:15]2[CH:20]=[CH:19][C:18]([O:21][CH3:22])=[CH:17][CH:16]=2)[C:12]2[CH:11]=[CH:10][N:9]=[CH:8][C:7]=2[C:6]=1[NH:23][C:32]1[CH:33]=[CH:34][C:35]([Si:37]([CH3:39])([CH3:38])[CH3:40])=[CH:36][C:31]=1[F:30])=[O:4]

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 672120873-Amino-1-(4-methoxy-benzyl)-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid methyl ester

Product 1

HCID 595966493-(2-Fluoro-4-trimethylsilanyl-phenylamino)-1-(4-methoxy-benzyl)-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid methyl esterYield 88%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
105 °C

Procedure

3-Amino-1-(4-methoxy-benzyl)-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid methyl ester (200 mg, 0.64 mmol) was dissolved in toluene (6 mL), to which Cs2CO3 (417 mg, 1.28 mmol) and trifluoro-methanesulfonic acid 2-fluoro-4-trimethylsilanyl-phenyl ester (263 mg, 0.83 mmol) were added and the mixture degassed with nitrogen before addition of Pd2dba3 (29 mg, 0.032 mmol) and Xantphos (37 mg, 0.064 mmol). The mixture was heated at 105° C. for 18 hours, allowed to cool to ambient temperature then partitioned between EtOAc (50 mL) and water (30 mL). The organic layer was isolated, dried (Na2SO4), filtered and evaporated to give a black oil. The oil was purified by flash column chromatography on silica (Si-PPC, cyclohexane:EtOAc, gradient 90:10 to 40:60) to provide the title compound as a pale brown solid (269 mg, 88%). LCMS (method B): RT=2.81 min, M+H+=478.

Workup

  1. additionwere added
  2. temperatureto cool to ambient temperature
  3. customthen partitioned between EtOAc (50 mL) and water (30 mL)
  4. customThe organic layer was isolated
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. customevaporated
  8. customto give a black oil
  9. customThe oil was purified by flash column chromatography on silica (Si-PPC, cyclohexane:EtOAc, gradient 90:10 to 40:60)

Sources & evidence

ORD record
ord-b99ccbfff41b4e269d725931b0c9d477
Source dataset
uspto-grants-2010_12
Patent number
US07855216B2

Reaction notes

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