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

HRID 2264923Notes

Reaction equation

HRID 2264923 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[N:14]([CH3:15])[C:13]2[C:12]([Cl:16])=[CH:11][N:10]=[CH:9][C:8]=2[C:7]=1[NH2:17])=[O:5])[CH3:2].[F:18][C:19]1[CH:24]=[C:23]([Si:25]([CH3:28])([CH3:27])[CH3:26])[CH:22]=[CH:21][C:20]=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[C:12]([Cl:16])=[CH:11][N:10]=[CH:9][C:8]=2[C:7]=1[NH:17][C:20]1[CH:21]=[CH:22][C:23]([Si:25]([CH3:27])([CH3:26])[CH3:28])=[CH:24][C:19]=1[F:18])=[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 595964653-Amino-7-chloro-1-methyl-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid ethyl ester

Product 1

HCID 595965317-Chloro-3-(2-fluoro-4-trimethylsilanyl-phenylamino)-1-methyl-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid ethyl esterYield 74.7%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Procedure

A degassed solution of 3-amino-7-chloro-1-methyl-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid ethyl ester (300 mg, 1.18 mmol), trifluoro-methanesulfonic acid 2-fluoro-4-trimethylsilanyl-phenyl ester (486 mg, 1.53 mmol), Pd2dba3 (54 mg, 0.06 mmol), Xantphos (68 mg, 0.118 mmol) and Cs2CO3 (770 mg, 2.36 mmol) in toluene (10 ml) was heated to reflux then stirred for 16 hours. The reaction mixture was cooled to ambient temperature then filtered through a pad of Celite® washing with toluene. The resultant solution was concentrated in vacuo to give an oil. The oil was purified by flash chromatography (SiO2, cyclohexane:ethyl acetate, gradient 95:5 to 90:10) to provide the title compound as a gum (370 mg, 74%). 1H NMR (CDCl3) 8.64 (1H, s), 8.31 (1H, s), 7.47 (1H, s, br), 7.23 (1H, dd, J=1.5, 110. Hz), 7.10 (1H, dd, J=1.0, 8.0 Hz), 6.97 (1H, t, J=8.0 Hz), 4.42 (2H, q, J=7.0 Hz), 4.35 (3H, s), 1.43 (3H, t, J=7.0 Hz), 0.29 (s, 9H).

Workup

  1. temperatureto reflux
  2. filtrationthen filtered through a pad of Celite®
  3. washwashing with toluene
  4. concentrationThe resultant solution was concentrated in vacuo
  5. customto give an oil
  6. customThe oil was purified by flash chromatography (SiO2, cyclohexane:ethyl acetate, gradient 95:5 to 90:10)

Sources & evidence

ORD record
ord-77e0a59c8e7f4f309539f42837fbcb77
Source dataset
uspto-grants-2010_12
Patent number
US07855216B2

Reaction notes

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