Sodium bis(trimethylsilyl)amide → HCID 58266623, compound

HRID 1888502Notes

Reaction equation

HRID 1888502 reaction equation
C[Si]([N-][Si](C)(C)C)(C)C.[Na+].[Br:11][C:12]1[C:13]([C:20]2[C:21](F)=[N:22][CH:23]=[C:24]([C:26]3[CH:31]=[CH:30][C:29]([CH2:32][N:33]4[CH2:38][CH2:37][CH2:36][CH2:35][CH2:34]4)=[CH:28][CH:27]=3)[CH:25]=2)=[C:14]([NH2:19])[CH:15]=[N:16][C:17]=1[Cl:18]>C1COCC1.O>[Br:11][C:12]1[C:13]2[C:20]3[CH:25]=[C:24]([C:26]4[CH:31]=[CH:30][C:29]([CH2:32][N:33]5[CH2:38][CH2:37][CH2:36][CH2:35][CH2:34]5)=[CH:28][CH:27]=4)[CH:23]=[N:22][C:21]=3[NH:19][C:14]=2[CH:15]=[N:16][C:17]=1[Cl:18]

Participants

5

Reactant 2

HCID 2724254Sodium bis(trimethylsilyl)amideHCID 58266759HCID 58266759, compound

Product 1

HCID 58266623HCID 58266623, compoundYield 17%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

Sodium bis(trimethylsilyl)amide (3.9 mL, 3.90 mmol) was added to a solution of 5′-bromo-6′-chloro-2-fluoro-5-(4-piperidin-1-ylmethyl-phenyl)-[3,4]bipyridinyl-3′-ylamine (187 mg, 0.39 mmol) in anhydrous THF (7.0 mL) and the resultant solution stirred at ambient temperature for 20 min. The reaction mixture was diluted with water (20 mL) and extracted with DCM: MeOH (4:1, 3×20 mL). The combined organic layer was dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo. The resultant residue was purified by flash chromatography (silica, 4 g column, ISCO, 0-15% MeOH in DCM) to afford the title compound as a beige powder (30 mg, 17%). 1H NMR (CDCl3, 400 MHz): 9.17 (d, J=2.0 Hz, 1H), 8.86 (d, J=2.0 Hz, 1H), 8.67 (s, 1H), 7.65 (d, J=7.5 Hz, 2H), 7.49 (d, J=7.5 Hz, 2H), 3.59 (s, 2H), 2.51-2.47 (m, 4H), 1.68-1.59 (m, 4H), 1.51-1.45 (m, 2H). LCMS (Method A): RT=7.10 min, M+H+=455/457.

Workup

  1. extractionextracted with DCM: MeOH (4:1, 3×20 mL)
  2. dry with materialThe combined organic layer was dried over anhydrous magnesium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customThe resultant residue was purified by flash chromatography (silica, 4 g column, ISCO, 0-15% MeOH in DCM)

Sources & evidence

ORD record
ord-613b196142e5494b9dcc8c7ff828803d
Source dataset
uspto-grants-2013_08
Patent number
US08501765B2

Reaction notes

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