Lithium bis(trimethylsilyl)amide → HCID 66599789, compound

HRID 1909054Notes

Reaction equation

HRID 1909054 reaction equation
C[Si](C)(C)N[Si](C)(C)C.[Li].[CH3:11][N:12]([CH3:36])[CH:13]([CH2:34][CH3:35])[CH2:14][CH2:15][NH:16][C:17]1[CH:33]=[CH:32][C:20]2[N:21]=[CH:22][N:23](COCC[Si](C)(C)C)[C:19]=2[CH:18]=1.[CH:37]1[C:46]2[C:41](=[CH:42][CH:43]=[CH:44][CH:45]=2)[C:40]([C:47]2[CH:48]=[C:49]([CH:52]=[CH:53][C:54]=2[O:55][CH3:56])[CH:50]=[O:51])=[CH:39][N:38]=1>C1COCC1>[CH3:36][N:12]([CH3:11])[CH:13]1[CH2:14][CH2:15][N:16]([C:17]2[CH:33]=[CH:32][C:20]3[N:21]=[C:22]([C:50]([C:49]4[CH:52]=[CH:53][C:54]([O:55][CH3:56])=[C:47]([C:40]5[C:41]6[C:46](=[CH:45][CH:44]=[CH:43][CH:42]=6)[CH:37]=[N:38][CH:39]=5)[CH:48]=4)=[O:51])[NH:23][C:19]=3[CH:18]=2)[CH2:35][CH2:34]1

Participants

5

Reactant 3

HCID 57426343Lithium bis(trimethylsilyl)amideHCID 66599670HCID 66599670, compoundHCID 86664355HCID 86664355, compound

Product 1

HCID 66599789HCID 66599789, compoundYield 17.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

To a cooled (−78° C.) 1M solution of lithium hexamethyldisilazane (0.88 mL, 0.88 mmol) in THF was added N3,N3-Dimethyl-N1-[3-(2-trimethylsilanyl-ethoxymethyl)-3H-benzoimidazol-5-yl]-pentane-1,3-diamine (82 mg, 0.22 mmol) in 1 mL THF. Solution turned bright orange. After 5 min, the reaction mixture was treated with 3-isoquinolin-4-yl-4-methoxy-benzaldehyde (58 mg, 0.22 mmol) in 1 mL THF. After 20 minutes, the reaction mixture was removed from cold bath, diluted with ethyl acetate and washed with saturated aqueous sodium bicarbonate. The organic phase was dried over Na2SO4, filtered and concentrated in vacuo. The residue was then dissolved in DCM: TFA. After 1 hour, the reaction mixture was concentrated and purified by HPLC (Deltapak C18, acetonitrile: 0.1% trifluoroacetic acid), then neutralized using PL-HCO3 SPE to obtain 19 mg [6-(4-dimethylamino-piperidin-1-yl)-1H-benzoimidazol-2-yl]-(3-isoquinolin-4-yl-4-methoxy-phenyl)-methanone in 17% yield. MS m/z 506.5 (M+H)+.

Workup

  1. waitAfter 20 minutes
  2. customthe reaction mixture was removed from cold bath
  3. additiondiluted with ethyl acetate
  4. washwashed with saturated aqueous sodium bicarbonate
  5. dry with materialThe organic phase was dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. dissolutionThe residue was then dissolved in DCM
  9. waitAfter 1 hour
  10. concentrationthe reaction mixture was concentrated
  11. custompurified by HPLC (Deltapak C18, acetonitrile: 0.1% trifluoroacetic acid)

Sources & evidence

ORD record
ord-d88a72e1191d41609c35cdaaa85ec389
Source dataset
uspto-grants-2013_12
Patent number
US08598217B2

Reaction notes

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