Sodium bis(trimethylsilyl)amide → HCID 58266480, compound

HRID 1888585Notes

Reaction equation

HRID 1888585 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:18]2[CH:19]=[C:20]([C:25]3[CH:30]=[C:29]([C:31]4[CH:32]=[N:33][N:34]([CH3:36])[CH:35]=4)[N:28]=[CH:27][C:26]=3[NH2:37])[C:21](F)=[N:22][CH:23]=2)[CH:6]=[C:7]([O:16][CH3:17])[C:8]=1[CH2:9][N:10]1[CH2:15][CH2:14][CH2:13][CH2:12][CH2:11]1.C[Si]([N-][Si](C)(C)C)(C)C.[Na+]>C1COCC1>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:18]2[CH:23]=[N:22][C:21]3[NH:37][C:26]4[CH:27]=[N:28][C:29]([C:31]5[CH:32]=[N:33][N:34]([CH3:36])[CH:35]=5)=[CH:30][C:25]=4[C:20]=3[CH:19]=2)[CH:6]=[C:7]([O:16][CH3:17])[C:8]=1[CH2:9][N:10]1[CH2:15][CH2:14][CH2:13][CH2:12][CH2:11]1

Participants

4

Reactant 2

HCID 2724254Sodium bis(trimethylsilyl)amideHCID 58266417HCID 58266417, compound

Product 1

HCID 58266480HCID 58266480, compoundYield 15%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of 5-(3,5-dimethoxy-4-piperidin-1-ylmethyl-phenyl)-2-fluoro-6′-(1-methyl-1H-pyrazol-4-yl)-[3,4]bipyridinyl-3′-ylamine (490 mg, 0.98 mmol) in anhydrous THF (16.7 mL) was added dropwise over 10 minutes to a solution of sodium bis(trimethylsilyl)amide (1N solution in THF, 2.9 mL, 2.9 mmol). After 30 minutes, the reaction was quenched by the addition of saturated aqueous potassium fluoride solution (5 mL) and concentrated under reduced pressure to afford a brown residue. The resultant brown residue was partitioned between ethyl acetate (75 mL) and water (50 mL). The organic phase was separated, dried over sodium sulfate, filtered and evaporated in vacuo to afford a residue that was purified by flash chromatography (silica, 50 g column, Biotage, 0-20% methanol in DCM) to afford the title compound as an off-white solid (69 mg, 15%). 1H NMR (CDCl3 plus CD3OD, 300 MHz): 8.86 (d, J=1.1 Hz, 1H), 8.84-8.80 (m, 2H), 8.37 (d, J=1.1 Hz, 1H), 8.09 (s, 1H), 8.06 (d, J=0.8 Hz, 1H), 6.91 (s, 2H), 4.01 (s, 3H), 3.96 (s, 6H), 3.74 (s, 2H), 2.64-2.50 (m, 4H), 1.65-1.56 (m, 4H), 1.49-1.37 (m, 2H).

Workup

  1. customthe reaction was quenched by the addition of saturated aqueous potassium fluoride solution (5 mL)
  2. concentrationconcentrated under reduced pressure
  3. customto afford a brown residue
  4. customThe resultant brown residue was partitioned between ethyl acetate (75 mL) and water (50 mL)
  5. customThe organic phase was separated
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. customevaporated in vacuo
  9. customto afford a residue that
  10. customwas purified by flash chromatography (silica, 50 g column, Biotage, 0-20% methanol in DCM)

Sources & evidence

ORD record
ord-7bb56ef8df164fa69bdd5c6e7f311478
Source dataset
uspto-grants-2013_08
Patent number
US08501765B2

Reaction notes

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