Hydrochloric Acid → 1-benzenesulfonyl-5-bromo-2-{[cyanomethyl-(toluene-4-sulfonyl)amino]methyl}-1H-pyrrolo[2,3-b]pyridine-3-carboxylic acid methyl ester

HRID 60214Notes

Reaction equation

HRID 60214 reaction equation
[H-].[Na+].[CH3:3][O:4][C:5]([C:7]1[C:15]2[C:10](=[N:11][CH:12]=[C:13]([Br:16])[CH:14]=2)[N:9]([S:17]([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)(=[O:19])=[O:18])[C:8]=1[CH2:26]Br)=[O:6].[C:28]([CH2:30][NH:31][S:32]([C:35]1[CH:40]=[CH:39][C:38]([CH3:41])=[CH:37][CH:36]=1)(=[O:34])=[O:33])#[N:29].Cl>CN(C=O)C>[CH3:3][O:4][C:5]([C:7]1[C:15]2[C:10](=[N:11][CH:12]=[C:13]([Br:16])[CH:14]=2)[N:9]([S:17]([C:20]2[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=2)(=[O:18])=[O:19])[C:8]=1[CH2:26][N:31]([CH2:30][C:28]#[N:29])[S:32]([C:35]1[CH:36]=[CH:37][C:38]([CH3:41])=[CH:39][CH:40]=1)(=[O:34])=[O:33])=[O:6]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 24758Sodium hydrideHCID 3113400N-Cyanomethyl-4-methyl-benzenesulfonamideHCID 582663771H-Pyrrolo[2,3-b]pyridine-3-carboxylic acid, 5-bromo-2-(bromomethyl)-1-(phenylsulfonyl)-, methyl ester

Product 1

HCID 582666181-benzenesulfonyl-5-bromo-2-{[cyanomethyl-(toluene-4-sulfonyl)amino]methyl}-1H-pyrrolo[2,3-b]pyridine-3-carboxylic acid methyl esterYield 94%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

Sodium hydride (11.7 g, 60% dispersion in mineral oil, 293 mmol) was added portionwise to a cooled (0° C.) solution of 1-benzenesulfonyl-5-bromo-2-bromomethyl-1H-pyrrolo[2,3-b]pyridine-3-carboxylic acid methyl ester (130 g, 266 mmol) and N-cyanomethyl-4-methyl-benzenesulfonamide (61.5 g, 293 mmol) in DMF (1.25 L). The reaction mixture was stirred at 0° C. for 15 minutes, then allowed to warm to ambient temperature and stirred for 1 hour. The reaction mixture was poured into a cooled, stirred solution of 2M hydrochloric acid (1.25 L). The resultant precipitate was collected by filtration (slow) and the cake washed with water, followed by methanol and then diethyl ether. The resulting cake was dried to afford the title compound as a grey solid (154 g, 94%). LCMS (Method B): RT=4.28 min, M+H+=617/619. 1H NMR (400 MHz, CDCl3): 8.49 (d, J=2.3 Hz, 1H), 8.42 (d, J=2.3 Hz, 1H), 8.33-8.33 (m, 2H), 7.78-7.76 (m, 2H), 7.64-7.64 (m, 1H), 7.55-7.54 (m, 2H), 7.34 (d, J=8.1 Hz, 2H), 5.43 (s, 2H), 4.28 (s, 2H), 3.96 (s, 3H), 2.43 (s, 3H).

Workup

  1. temperatureto warm to ambient temperature
  2. stirringstirred for 1 hour
  3. additionThe reaction mixture was poured into a cooled
  4. filtrationThe resultant precipitate was collected by filtration (slow)
  5. washthe cake washed with water
  6. customThe resulting cake was dried

Sources & evidence

ORD record
ord-853fb808fe3e4691bfb5ee8dc879afb1
Source dataset
uspto-grants-2016_09
Patent number
US09440976B2

Reaction notes

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