Lithium Hexamethyldisilazide → 8-(Benzenesulfonyl)-12-bromo-3-hydroxy-5,8,10-triazatricyclo[7.4.0.02,7]trideca-1(9),2,4,6,10,12-hexaene-4-carbonitrile

HRID 1505853Notes

Reaction equation

HRID 1505853 reaction equation
C[Si]([N-][Si](C)(C)C)(C)C.[Li+].C[O:12][C:13]([C:15]1[C:23]2[C:18](=[N:19][CH:20]=[C:21]([Br:24])[CH:22]=2)[N:17]([S:25]([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)(=[O:27])=[O:26])[C:16]=1[CH2:34][N:35]([CH2:46][C:47]#[N:48])S(C1C=CC(C)=CC=1)(=O)=O)=O>C1COCC1>[C:28]1([S:25]([N:17]2[C:16]3[CH:34]=[N:35][C:46]([C:47]#[N:48])=[C:13]([OH:12])[C:15]=3[C:23]3[CH:22]=[C:21]([Br:24])[CH:20]=[N:19][C:18]2=3)(=[O:27])=[O:26])[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=1

Participants

4

Reactant 2

HCID 2733832Lithium HexamethyldisilazideHCID 582666181-benzenesulfonyl-5-bromo-2-{[cyanomethyl-(toluene-4-sulfonyl)amino]methyl}-1H-pyrrolo[2,3-b]pyridine-3-carboxylic acid methyl ester

Product 1

HCID 582664728-(Benzenesulfonyl)-12-bromo-3-hydroxy-5,8,10-triazatricyclo[7.4.0.02,7]trideca-1(9),2,4,6,10,12-hexaene-4-carbonitrileYield 60%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-10 °C

Procedure

Lithium bis(trimethylsilyl)amide (2.34 mL of a 1N solution in THF, 2.34 mmol) was added dropwise to a cooled (−78° C.) suspension of 1-benzenesulfonyl-5-bromo-2-{[cyanomethyl-(toluene-4-sulfonyl)amino]methyl}-1H-pyrrolo[2,3-b]pyridine-3-carboxylic acid methyl ester (0.48 g, 0.78 mmol) in dry THF (12 mL). The reaction mixture was allowed to slowly warm to −10° C. and then quenched with saturated aqueous ammonium chloride solution (8 mL). The reaction mixture was diluted with water and washed with DCM (2×10 mL). The combined organic phase was dried over anhydrous magnesium sulfate and concentrated in vacuo. The resultant residue was purified by flash chromatography (silica, 5 g cartridge, Si-SPE, 10-100% THF in DCM) to afford the title compound as a brown solid (0.20 g, 60%). LCMS (Method B): RT=3.83 min, M+H+=429/431.

Workup

  1. temperaturea cooled
  2. customquenched with saturated aqueous ammonium chloride solution (8 mL)
  3. additionThe reaction mixture was diluted with water
  4. washwashed with DCM (2×10 mL)
  5. dry with materialThe combined organic phase was dried over anhydrous magnesium sulfate
  6. concentrationconcentrated in vacuo
  7. customThe resultant residue was purified by flash chromatography (silica, 5 g cartridge, Si-SPE, 10-100% THF in DCM)

Sources & evidence

ORD record
ord-dc97bff377644160a8ed2790e14d62b5
Source dataset
uspto-grants-2015_12
Patent number
US09216980B2

Reaction notes

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