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 60215Notes

Reaction equation

HRID 60215 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 72.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-10 °C

Procedure

Lithium bis(trimethylsilyl)amide (800 mL of a 1N solution in THF, 800 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 (154 g, 250 mmol) in dry THF (1.25 L). 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 beige solid (77.6 g, 72%). LCMS (Method B): RT=3.83 min, M+H+=429/431. 1H NMR (400 MHz, DMSO-d6): 9.22 (s, 1H), 8.83 (d, J=2.3 Hz, 1H), 8.81 (d, J=2.3 Hz, 1H), 8.19-8.16 (m, 2H), 7.75-7.74 (m, 1H), 7.65-7.59 (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-2554c65b0ffb47c39f17ed26e0e08285
Source dataset
uspto-grants-2016_09
Patent number
US09440976B2

Reaction notes

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