Ammonium Chloride → [6-(2-chloro-benzylamino)-2-fluoro-pyridin-3-yl]-(1-triisopropylsilanyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-methanol

HRID 1952152Notes

Reaction equation

HRID 1952152 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([NH:9][CH2:10][C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=2[Cl:17])=[N:6][C:7]=1[F:8].C([Li])CCC.C([Li])(C)(C)C.[CH:28]([Si:31]([CH:46]([CH3:48])[CH3:47])([CH:43]([CH3:45])[CH3:44])[N:32]1[C:36]2=[N:37][CH:38]=[CH:39][CH:40]=[C:35]2[C:34]([CH:41]=[O:42])=[CH:33]1)([CH3:30])[CH3:29].[Cl-].[NH4+]>O1CCCC1>[Cl:17][C:12]1[CH:13]=[CH:14][CH:15]=[CH:16][C:11]=1[CH2:10][NH:9][C:5]1[N:6]=[C:7]([F:8])[C:2]([CH:41]([C:34]2[C:35]3[C:36](=[N:37][CH:38]=[CH:39][CH:40]=3)[N:32]([Si:31]([CH:43]([CH3:45])[CH3:44])([CH:46]([CH3:48])[CH3:47])[CH:28]([CH3:29])[CH3:30])[CH:33]=2)[OH:42])=[CH:3][CH:4]=1

Participants

7

Reactant 5

HCID 25517Ammonium ChlorideHCID 497589651H-Pyrrolo[2,3-B]pyridine-3-carboxaldehyde, 1-[tris(1-methylethyl)silyl]-HCID 57619357(5-Bromo-6-fluoro-pyridin-2-yl)-(2-chloro-benzyl)-amineHCID 178418306HCID 178418306, compoundHCID 178418339Butyllithium

Product 1

HCID 68804150[6-(2-chloro-benzylamino)-2-fluoro-pyridin-3-yl]-(1-triisopropylsilanyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-methanolYield 17.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

To (5-bromo-6-fluoro-pyridin-2-yl)-(2-chloro-benzyl)-amine (571, 0.635 g, 2.01 mmol, prepared as described in Example 60, Scheme 177) in tetrahydrofuran (25.0 mL) under an atmosphere of nitrogen at −78° C., a solution of n-butyllithium (2.50 M in hexane, 0.80 mL) was added slowly. After 20 minutes, tert-butyllithium (1.7 M in hexane, 2.40 mL) was added to the reaction and after 30 minutes, 1-triisopropylsilanyl-1H-pyrrolo[2,3-b]pyridine-3-carbaldehyde (47, 0.575 g, 1.90 mmol, prepared as described in Example 18) in tetrahydrofuran (8.0 mL) was added to the reaction. The reaction mixture was stirred at −78° C. for 60 minutes, then allowed to warm to room temperature for another 10 minutes. The reaction mixture was poured into aqueous ammonium chloride and extracted with ethyl acetate. The organic layer was washed with brine, dried over sodium sulfate, concentrated and purified by silica gel column chromatography eluting with 20% to 100% ethyl acetate in hexane to give the desired compound (606, 0.180 g, 17.6%). MS (ESI) [M+H+]+=539.2.

Workup

  1. temperatureto warm to room temperature for another 10 minutes
  2. extractionextracted with ethyl acetate
  3. washThe organic layer was washed with brine
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated
  6. custompurified by silica gel column chromatography
  7. washeluting with 20% to 100% ethyl acetate in hexane

Sources & evidence

ORD record
ord-b37841161dfe4218af4c99a5c7d818d4
Source dataset
uspto-grants-2013_03
Patent number
US08404700B2

Reaction notes

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