Lithium Hexamethyldisilazide → HCID 58364995, compound

HRID 60224Notes

Reaction equation

HRID 60224 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]([F: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]([F: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 583650531-Benzenesulfonyl-5-fluoro-2-{[cyanomethyl-(toluene-4-sulfonyl)amino]-methyl}-1H-pyrrolo[2,3-b]pyridine-3-carboxylic acid methyl ester

Product 1

HCID 58364995HCID 58364995, compoundYield 75.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-10 °C

Procedure

Lithium bis(trimethylsilyl)amide (100 mL of a 1N solution in THF, 100 mmol) was added dropwise to a cooled (−78° C.) suspension of 1-benzenesulfonyl-5-fluoro-2-{[cyanomethyl-(toluene-4-sulfonyl)amino]methyl}-1H-pyrrolo[2,3-b]pyridine-3-carboxylic acid methyl ester (16.5 g, 29.6 mmol) in dry THF (150 mL). The reaction mixture was allowed to slowly warm to −10° C. then slowly quenched into cold 1M hydrochloric acid. The layers were separated and the aqueous layer further extracted with THF. The combined organic layer was washed with brine, dried (Na2SO4), filtered and evaporated. The resultant residue was triturated with methanol then acetone and air dried to afford the title compound as a brown solid (8.2 g, 75%). 1H NMR (400 MHz, DMSO-d6): 9.25 (s, 1H), 8.76 (dd, J=2.8, 1.3 Hz, 1H), 8.50 (dd, J=8.2, 2.8 Hz, 1H), 8.20-8.17 (m, 2H), 7.75-7.75 (m, 1H), 7.63-7.62 (m, 2H).

Workup

  1. temperaturea cooled
  2. customthen slowly quenched into cold 1M hydrochloric acid
  3. customThe layers were separated
  4. extractionthe aqueous layer further extracted with THF
  5. washThe combined organic layer was washed with brine
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. customevaporated
  9. customThe resultant residue was triturated with methanol
  10. dry with materialacetone and air dried

Sources & evidence

ORD record
ord-b81ef6dcbf8c407791fe965b5dcf72d2
Source dataset
uspto-grants-2016_09
Patent number
US09440976B2

Reaction notes

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