2-Amino-5-bromopyridine → alpha-(6-Amino-3-pyridinyl)-5-chloro-1-(phenylsulfonyl)-1H-pyrrolo(2,3-b)pyridine-3-methanol

HRID 1024285Notes

Reaction equation

HRID 1024285 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5](Br)=[CH:4][N:3]=1.C([Li])CCC.Cl[Si](C)(C)CC[Si](Cl)(C)C.[C:24]1([S:30]([N:33]2[C:37]3=[N:38][CH:39]=[C:40]([Cl:42])[CH:41]=[C:36]3[C:35]([CH:43]=[O:44])=[CH:34]2)(=[O:32])=[O:31])[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1>O1CCCC1.O>[NH2:1][C:2]1[N:3]=[CH:4][C:5]([CH:43]([C:35]2[C:36]3[C:37](=[N:38][CH:39]=[C:40]([Cl:42])[CH:41]=3)[N:33]([S:30]([C:24]3[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=3)(=[O:32])=[O:31])[CH:34]=2)[OH:44])=[CH:6][CH:7]=1

Participants

7

Reactant 4

HCID 706222-Amino-5-bromopyridineHCID 835521,2-Bis(chlorodimethylsilyl)ethaneHCID 497590321H-Pyrrolo[2,3-B]pyridine-3-carboxaldehyde, 5-chloro-1-(phenylsulfonyl)-HCID 178418339Butyllithium3×

Product 1

HCID 57619405alpha-(6-Amino-3-pyridinyl)-5-chloro-1-(phenylsulfonyl)-1H-pyrrolo(2,3-b)pyridine-3-methanolYield 50.9%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To 2-amino-5-bromopyridine (15, 3.10 g, 17.9 mmol) in tetrahydrofuran (80.0 mL) under an atmosphere of nitrogen at −78° C., a solution n-butyllithium (2.50M in hexane, 7.10 mL) was added slowly. After 30 minutes, 1,2-bis-(chloro-dimethyl-silanyl)-ethane (3.90 g dissolved in tetrahydrofuran 20.0 mL, 18.1 mmol) was added to the reaction mixture slowly, and then allowed to warm to room temperature for 1 hour. The reaction was cooled to −78° C. followed by adding a solution of n-butyllithium (2.50M in Hexane, 7.10 mL). The reaction mixture was stirred at −78° C. for 30 minutes, then allowed to warm to room temperature for 60 minutes. The reaction mixture was cooled to −78° C., followed by adding a solution of n-butyllithium (2.50M in Hexane, 7.50 mL) slowly. After 60 minutes, 1-benzenesulfonyl-5-chloro-1H-pyrrolo[2,3-b]pyridine-3-carbaldehyde (597, 1.90 g in 30 mL tetrahydrofuran, 5.92 mmol) was added to the reaction mixture. The reaction mixture was stirred at −78° C. for 2 hours, then allowed to warm to room temperature for 1 hour. The reaction was poured into water and extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated and purified by silica gel column chromatography eluting with 2% to 20% methanol in dichloromethane to give the desired compound (598, 1.25 g, 50.9%). MS (ESI) [M+H+]+=415.2.

Workup

  1. temperatureThe reaction was cooled to −78° C.
  2. temperatureto warm to room temperature for 60 minutes
  3. temperatureThe reaction mixture was cooled to −78° C.
  4. waitAfter 60 minutes
  5. stirringThe reaction mixture was stirred at −78° C. for 2 hours
  6. temperatureto warm to room temperature for 1 hour
  7. extractionextracted with ethyl acetate
  8. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  9. filtrationfiltered
  10. concentrationThe filtrate was concentrated
  11. custompurified by silica gel column chromatography
  12. washeluting with 2% to 20% methanol in dichloromethane

Sources & evidence

ORD record
ord-9cab01a154234cc787f93388136299e7
Source dataset
uspto-grants-2014_05
Patent number
US08722702B2

Reaction notes

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