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

HRID 2264934Notes

Reaction equation

HRID 2264934 reaction equation
Br[CH2:2][CH2:3][CH2:4][O:5][Si:6]([CH:13]([CH3:15])[CH3:14])([CH:10]([CH3:12])[CH3:11])[CH:7]([CH3:9])[CH3:8].[CH2:16]([O:18][C:19]([C:21]1[NH:29][C:28]2[CH:27]=[CH:26][N:25]=[CH:24][C:23]=2[C:22]=1[NH:30][C:31]1[CH:36]=[CH:35][C:34]([I:37])=[CH:33][C:32]=1[F:38])=[O:20])[CH3:17].C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C=O)C.O>[CH2:16]([O:18][C:19]([C:21]1[N:29]([CH2:2][CH2:3][CH2:4][O:5][Si:6]([CH:13]([CH3:15])[CH3:14])([CH:10]([CH3:12])[CH3:11])[CH:7]([CH3:9])[CH3:8])[C:28]2[CH:27]=[CH:26][N:25]=[CH:24][C:23]=2[C:22]=1[NH:30][C:31]1[CH:36]=[CH:35][C:34]([I:37])=[CH:33][C:32]=1[F:38])=[O:20])[CH3:17]

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 23510097(3-Bromopropoxy)tri(propan-2-yl)silaneHCID 672119973-(2-fluoro-4-iodo-phenylamino)-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid ethyl ester

Product 1

HCID 595964883-(2-Fluoro-4-iodo-phenylamino)-1-(3-triisopropylsilanyloxy-propyl)-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid ethyl esterYield 44%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

(3-Bromo-propoxy)-triisopropyl-silane (209 mg, 0.71 mmol) was dissolved in DMF (5 ml) and 3-(2-fluoro-4-iodophenylamino)-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid ethyl ester (250 mg, 0.59 mmol) was added, followed by cesium carbonate (250 mg, 0.77 mmol). The mixture was heated at 80° C. under nitrogen for 3 hours, then allowed to cool, diluted with water and extracted with dichloromethane (×2). The combined organic layers were washed with 20% aqueous lithium chloride solution, dried over magnesium sulfate then concentrated in vacuo. Purification of the resultant residue by flash chromatography (Si-PPC, dichloromethane:methanol gradient 1:0 to 99:1) gave the title compound as a yellow oil (109 mg, 44%). LCMS (method B): RT 3.41, M+H+ 640.

Workup

  1. temperatureto cool
  2. extractionextracted with dichloromethane (×2)
  3. washThe combined organic layers were washed with 20% aqueous lithium chloride solution
  4. dry with materialdried over magnesium sulfate
  5. concentrationthen concentrated in vacuo
  6. customPurification of the resultant residue by flash chromatography (Si-PPC, dichloromethane:methanol gradient 1:0 to 99:1)

Sources & evidence

ORD record
ord-f3409f5d826a49039d9e6223944d4376
Source dataset
uspto-grants-2010_12
Patent number
US07855216B2

Reaction notes

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