2-Bromopyridine → HCID 89630048, compound

HRID 882161Notes

Reaction equation

HRID 882161 reaction equation
[CH3:1][C:2](=[CH2:38])[C:3]([NH:5][C:6]1[CH:11]=[CH:10][CH:9]=[C:8]([C:12]2[C:13]3[C:20](B4OC(C)(C)C(C)(C)O4)=[CH:19][N:18]([CH2:30][O:31][CH2:32][CH2:33][Si:34]([CH3:37])([CH3:36])[CH3:35])[C:14]=3[N:15]=[CH:16][N:17]=2)[CH:7]=1)=[O:4].Br[C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][N:41]=1.C(=O)([O-])[O-].[Na+].[Na+]>CN(C)C=O>[N:41]1[CH:42]=[CH:43][CH:44]=[CH:45][C:40]=1[C:20]1[C:13]2[C:12]([C:8]3[CH:7]=[C:6]([NH:5][C:3](=[O:4])[C:2]([CH3:1])=[CH2:38])[CH:11]=[CH:10][CH:9]=3)=[N:17][CH:16]=[N:15][C:14]=2[N:18]([CH2:30][O:31][CH2:32][CH2:33][Si:34]([CH3:36])([CH3:35])[CH3:37])[CH:19]=1

Participants

5

Reactant 3

HCID 79732-BromopyridineHCID 10340Sodium CarbonateHCID 89630020HCID 89630020, compound

Product 1

HCID 89630048HCID 89630048, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of 2-methyl-N-[3-[5-(tetramethyl-1,3,2-dioxaborolan-2-yl)-7-[[2-(trimethylsilyl)ethoxy]methyl]-7H-pyrrolo[2,3-d]pyrimidin-4-yl]phenyl]prop-2-enamide (200 mg, 0.370 mmol) in N,N-dimethylformamide (3.0 mL) under nitrogen, was added Pd(dppf)Cl2CH2Cl2 (16 mg, 0.020 mmol), 2-bromopyridine (60 mg, 0.38 mmol), and a solution of sodium carbonate (120 mg, 1.13 mmol in water, 1 mL). The resulting solution was stirred for 2 hours at 80° C. before being cooled and extracted with ethyl acetate (×3). The organic layers were combined, washed with brine, dried with anhydrous sodium sulfate, filtered and concentrated in vacuo. The reaction was then purified by chromatography using silica gel, eluting with 0-100% EtOAc/petroleum ether. The product was collected and concentrated in vacuo to afford N-(3-(5-(pyridin-2-yl)-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl)phenyl)methacrylamide as a yellow oil. LRMS (ESI) calc'd for C27H32N5O2Si [M+H]+: 486, found 486.

Workup

  1. temperaturebefore being cooled
  2. extractionextracted with ethyl acetate (×3)
  3. washwashed with brine
  4. dry with materialdried with anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe reaction was then purified by chromatography
  8. washeluting with 0-100% EtOAc/petroleum ether
  9. customThe product was collected
  10. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-3770b76a9cf641fc9f56d91763abc041
Source dataset
uspto-grants-2015_03
Patent number
US08993756B2

Reaction notes

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