Sodium bis(trimethylsilyl)amide → HCID 58266315, compound

HRID 1506044Notes

Reaction equation

HRID 1506044 reaction equation
C[Si]([N-][Si](C)(C)C)(C)C.[Na+].[CH2:11]([N:13]1[CH2:18][CH2:17][C:16]2[S:19][C:20]([C:22]3[CH:23]=[C:24]([C:29]4[CH:34]=[C:33]([C:35]5[CH:36]=[N:37][N:38]([CH3:40])[CH:39]=5)[N:32]=[CH:31][C:30]=4[NH2:41])[C:25](F)=[N:26][CH:27]=3)=[CH:21][C:15]=2[CH2:14]1)[CH3:12]>C1COCC1>[CH2:11]([N:13]1[CH2:18][CH2:17][C:16]2[S:19][C:20]([C:22]3[CH:27]=[N:26][C:25]4[NH:41][C:30]5[CH:31]=[N:32][C:33]([C:35]6[CH:36]=[N:37][N:38]([CH3:40])[CH:39]=6)=[CH:34][C:29]=5[C:24]=4[CH:23]=3)=[CH:21][C:15]=2[CH2:14]1)[CH3:12]

Participants

4

Reactant 2

HCID 2724254Sodium bis(trimethylsilyl)amideHCID 58266370HCID 58266370, compound

Product 1

HCID 58266315HCID 58266315, compoundYield 16%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of sodium bis(trimethylsilyl)amide (1N solution in THF, 4.5 mL, 4.5 mmol) was added dropwise over 10 minutes to a solution of 5-(5-ethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-fluoro-6′-(1-methyl-1H-pyrazol-4-yl)-[3,4]bipyridinyl-3′-ylamine (638 mg, 1.50 mmol) in anhydrous THF (26 mL). After 30 minutes, the reaction was quenched by the addition of aqueous saturated aqueous potassium fluoride solution (10 mL). The resultant brown solution was partitioned between DCM (75 mL) and brine (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, 0-15% methanol in DCM) to afford the title compound as a white solid (96 mg, 16%). 1H NMR (CDCl3 plus CD3OD, 300 MHz): 8.82 (s, 1H), 8.76 (d, J=2.2 Hz, 1H), 8.66 (d, J=2.2 Hz, 1H), 8.29 (s, 1H), 8.07 (s, 1H), 8.05 (s, 1H), 7.11 (s, 1H), 4.00 (s, 3H), 3.64 (s, 2H), 3.02-2.95 (m, 2H), 2.93-2.86 (m, 2H), 2.70 (q, J=7.2 Hz, 2H), 1.24 (t, J=7.2 Hz, 3H).

Workup

  1. customthe reaction was quenched by the addition of aqueous saturated aqueous potassium fluoride solution (10 mL)
  2. customThe resultant brown solution was partitioned between DCM (75 mL) and brine (50 mL)
  3. customThe organic phase was separated
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. customevaporated in vacuo
  7. customto afford a residue that
  8. customwas purified by flash chromatography (silica, 50 g column, Biotage, 0-15% methanol in DCM)

Sources & evidence

ORD record
ord-440c9370d9fb4b63a590f4a68073f27a
Source dataset
uspto-grants-2015_12
Patent number
US09216980B2

Reaction notes

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