Lithium Hexamethyldisilazide → 9-Benzenesulfonyl-5-hydroxy-9H-dipyrido[2,3-b;4',3'-d]pyrrole-6-carbonitrile

HRID 1505849Notes

Reaction equation

HRID 1505849 reaction equation
C[Si]([N-][Si](C)(C)C)(C)C.[Li+].CO[C:13]([C:15]1[C:23]2[C:18](=[N:19][CH:20]=[CH:21][CH:22]=2)[N:17]([S:24]([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)(=[O:26])=[O:25])[C:16]=1[CH2:33][N:34]([CH2:45][C:46]#[N:47])S(C1C=CC(C)=CC=1)(=O)=O)=[O:14]>C1COCC1>[C:27]1([S:24]([N:17]2[C:16]3[CH:33]=[N:34][C:45]([C:46]#[N:47])=[C:13]([OH:14])[C:15]=3[C:23]3[CH:22]=[CH:21][CH:20]=[N:19][C:18]2=3)(=[O:25])=[O:26])[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=1

Participants

4

Reactant 2

HCID 2733832Lithium HexamethyldisilazideHCID 58266773HCID 58266773, compound

Product 1

HCID 582663029-Benzenesulfonyl-5-hydroxy-9H-dipyrido[2,3-b;4',3'-d]pyrrole-6-carbonitrile

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-30 °C

Procedure

Lithium bis(trimethylsilyl)amide (9.6 mL, 1N solution in THF, 9.60 mmol) was added dropwise to a cooled (−78° C.) suspension of 1-benzenesulfonyl-2-{[cyanomethyl(toluene-4-sulfonyl)amino]methyl}-1H-pyrrolo[2,3-b]pyridine-3-carboxylic acid methyl ester (1.72 g, 3.19 mmol) in dry THF (50 mL). The reaction mixture was allowed to warm to −30° C., stirred at −30° C. for 2 h, before warming to ambient temperature. The reaction mixture was quenched with saturated aqueous ammonium chloride solution (30 mL) and water (50 mL). The aqueous phase was extracted with DCM (2×20 mL) and the combined organic phase was washed with brine and concentrated in vacuo. The resultant solid was triturated with THF (2×4 mL) to afford the title compound. The filtrate was purified by flash chromatography (silica, 5 g column, Si-SPE, ethyl acetate then 10-20% MeOH in DCM) to afford the remaining title compound. The two batches of material were combined to afford a yellow solid (1.03 g, 90%). LCMS (Method B): RT=3.26 min, M+H+=351.

Workup

  1. temperaturea cooled
  2. temperaturebefore warming to ambient temperature
  3. customThe reaction mixture was quenched with saturated aqueous ammonium chloride solution (30 mL) and water (50 mL)
  4. extractionThe aqueous phase was extracted with DCM (2×20 mL)
  5. washthe combined organic phase was washed with brine
  6. concentrationconcentrated in vacuo
  7. customThe resultant solid was triturated with THF (2×4 mL)

Sources & evidence

ORD record
ord-31dd8f1e93494d85b0b02cb222a75b28
Source dataset
uspto-grants-2015_12
Patent number
US09216980B2

Reaction notes

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