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

HRID 2264916Notes

Reaction equation

HRID 2264916 reaction equation
[CH3:1][O:2][C:3]([C:5]1[N:13]([CH2:14][CH2:15][O:16][Si:17]([CH:24]([CH3:26])[CH3:25])([CH:21]([CH3:23])[CH3:22])[CH:18]([CH3:20])[CH3:19])[C:12]2[CH:11]=[CH:10][N:9]=[CH:8][C:7]=2[C:6]=1[NH2:27])=[O:4].[F:28][C:29]1[CH:34]=[C:33]([Si:35]([CH3:38])([CH3:37])[CH3:36])[CH:32]=[CH:31][C:30]=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]>[CH3:1][O:2][C:3]([C:5]1[N:13]([CH2:14][CH2:15][O:16][Si:17]([CH:24]([CH3:26])[CH3:25])([CH:18]([CH3:20])[CH3:19])[CH:21]([CH3:23])[CH3:22])[C:12]2[CH:11]=[CH:10][N:9]=[CH:8][C:7]=2[C:6]=1[NH:27][C:30]1[CH:31]=[CH:32][C:33]([Si:35]([CH3:37])([CH3:36])[CH3:38])=[CH:34][C:29]=1[F:28])=[O:4]

Participants

8

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 595966513-Amino-1-(2-triisopropylsilanyloxy-ethyl)-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid methyl ester

Product 1

HCID 595966283-(2-Fluoro-4-trimethylsilanyl-phenylamino)-1-(2-triisopropylsilanyloxy-ethyl)-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid methyl esterYield 88.4%

Reagents, catalysts & solvents 3

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

Procedure

A degassed solution of 3-amino-1-(2-triisopropylsilanyloxy-ethyl)-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid methyl ester (1.41 g, 3.61 mmol), trifluoro-methanesulfonic acid 2-fluoro-4-trimethylsilanyl-phenyl ester (1.48 g, 4.69 mmol), Pd2dba3 (165 mg, 0.18 mmol), Xantphos (208 mg, 0.36 mmol) and Cs2CO3 (2.35 g, 7.21 mmol) in toluene (30 ml) was heated to reflux then stirred for 16 hours. The reaction mixture was cooled to ambient temperature then diluted with EtOAc and filtered through a pad of celite. The resultant solution was concentrated in vacuo to give a black oil. The oil was purified by flash chromatography (Si-PPC, pentane:ether, gradient 100:0 to 0:100) to provide the title compound as a yellow oil (1.78 g, 88%). LCMS (method B): RT=3.76 min, M+H+=558.

Workup

  1. temperatureto reflux
  2. filtrationfiltered through a pad of celite
  3. concentrationThe resultant solution was concentrated in vacuo
  4. customto give a black oil
  5. customThe oil was purified by flash chromatography (Si-PPC, pentane:ether, gradient 100:0 to 0:100)

Sources & evidence

ORD record
ord-b4017f2083ae4854a46baa80017785e9
Source dataset
uspto-grants-2010_12
Patent number
US07855216B2

Reaction notes

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