4-Toluenesulfonyl chloride → 7-Ethynyl-2-(4-isopropylsulfonylphenyl)-5-(p-tolylsulfonyl)pyrrolo[2,3-b]pyrazine

HRID 467499Notes

Reaction equation

HRID 467499 reaction equation
[H-].[Na+].[C:3]([C:5]1[C:13]2[C:8](=[N:9][CH:10]=[C:11]([C:14]3[CH:19]=[CH:18][C:17]([S:20]([CH:23]([CH3:25])[CH3:24])(=[O:22])=[O:21])=[CH:16][CH:15]=3)[N:12]=2)[NH:7][CH:6]=1)#[CH:4].[S:26](Cl)([C:29]1[CH:35]=[CH:34][C:32]([CH3:33])=[CH:31][CH:30]=1)(=[O:28])=[O:27]>CN(C=O)C>[C:3]([C:5]1[C:13]2[C:8](=[N:9][CH:10]=[C:11]([C:14]3[CH:15]=[CH:16][C:17]([S:20]([CH:23]([CH3:25])[CH3:24])(=[O:22])=[O:21])=[CH:18][CH:19]=3)[N:12]=2)[N:7]([S:26]([C:29]2[CH:35]=[CH:34][C:32]([CH3:33])=[CH:31][CH:30]=2)(=[O:28])=[O:27])[CH:6]=1)#[CH:4]

Participants

5

Reactant 3

HCID 73974-Toluenesulfonyl chlorideHCID 24758Sodium hydrideHCID 866624437-Ethynyl-2-(4-isopropylsulfonylphenyl)-5H-pyrrolo[2,3-b]pyrazine

Product 1

HCID 866624447-Ethynyl-2-(4-isopropylsulfonylphenyl)-5-(p-tolylsulfonyl)pyrrolo[2,3-b]pyrazine

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A 60% dispersion of sodium hydride in mineral oil (19.79 mg, 0.5164 mmol) was added slowly to a stirred solution of 7-ethynyl-2-(4-isopropylsulfonylphenyl)-5H-pyrrolo[2,3-b]pyrazine (140 mg, 0.4303 mmol) in DMF (1.2 mL) at 0° C. The reaction mixture was stirred at this temperature for 20 minutes then tosyl chloride (82.04 mg, 0.4303 mmol) was added and reaction mixture allowed to warm to ambient temperature over 16 hours. The reaction mixture was quenched by the slow addition of water (30 mL) and the mixture stirred for 20 minutes. The aqueous layer was extracted with EtOAc (×3) and the combined organic extracts dried (MgSO4), filtered and concentrated in vacuo. The residue was triturated form DCM/diethyl ether and the resultant precipitate isolated by filtration to give the sub-tile compound as an off-white solid (112.6 mg, 59% Yield). 1H NMR (400.0 MHz, DMSO) δ 1.19 (d, 6H), 2.37 (s, 3H), 3.45-3.50 (m, 1H), 4.55 (s, 1H), 7.49 (d, 2H), 8.01 (d, 2H), 8.08 (d, 2H), 8.41 (d, 2H), 8.75 (s, 1H) and 9.22 (s, 1H) ppm; MS (ES+) 480.0.

Workup

  1. customreaction mixture
  2. customThe reaction mixture was quenched by the slow addition of water (30 mL)
  3. stirringthe mixture stirred for 20 minutes
  4. extractionThe aqueous layer was extracted with EtOAc (×3)
  5. dry with materialthe combined organic extracts dried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue was triturated form DCM/diethyl ether

Sources & evidence

ORD record
ord-4b45de259a3d4368815d794c6b59d5d8
Source dataset
uspto-grants-2014_01
Patent number
US08623869B2

Reaction notes

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