2,3-Dichloro-5,6-dicyano-1,4-benzoquinone → 1-(5-(5-chloro-2-(1-methyl-1H-pyrazol-4-yl)-1-tosyl-1H-pyrrolo[2,3-b]pyridin-4-yl)thiazol-2-yl)cyclobutanamine

HRID 2362731Notes

Reaction equation

HRID 2362731 reaction equation
[Cl:1][C:2]1[C:3]([C:27]2[S:31][C:30]([C:32]3([NH:36]CC4C=CC(OC)=CC=4)[CH2:35][CH2:34][CH2:33]3)=[N:29][CH:28]=2)=[C:4]2[CH:10]=[C:9]([C:11]3[CH:12]=[N:13][N:14]([CH3:16])[CH:15]=3)[N:8]([S:17]([C:20]3[CH:26]=[CH:25][C:23]([CH3:24])=[CH:22][CH:21]=3)(=[O:19])=[O:18])[C:5]2=[N:6][CH:7]=1.ClC1C(=O)C(C#N)=C(C#N)C(=O)C=1Cl>ClCCl.O>[Cl:1][C:2]1[C:3]([C:27]2[S:31][C:30]([C:32]3([NH2:36])[CH2:33][CH2:34][CH2:35]3)=[N:29][CH:28]=2)=[C:4]2[CH:10]=[C:9]([C:11]3[CH:12]=[N:13][N:14]([CH3:16])[CH:15]=3)[N:8]([S:17]([C:20]3[CH:26]=[CH:25][C:23]([CH3:24])=[CH:22][CH:21]=3)(=[O:19])=[O:18])[C:5]2=[N:6][CH:7]=1

Participants

5

Reactant 2

HCID 67752,3-Dichloro-5,6-dicyano-1,4-benzoquinone2×HCID 670035991-(5-(5-chloro-2-(1-methyl-1H-pyrazol-4-yl)-1-tosyl-1H-pyrrolo[2,3-b]pyridin-4-yl)thiazol-2-yl)-N-(4-methoxybenzyl)cyclobutanamine

Product 1

HCID 670037141-(5-(5-chloro-2-(1-methyl-1H-pyrazol-4-yl)-1-tosyl-1H-pyrrolo[2,3-b]pyridin-4-yl)thiazol-2-yl)cyclobutanamine

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

A solution of 1-(5-(5-chloro-2-(1-methyl-1H-pyrazol-4-yl)-1-tosyl-1H-pyrrolo[2,3-b]pyridin-4-yl)thiazol-2-yl)-N-(4-methoxybenzyl)cyclobutanamine (500 mg, 0.758 mmol) (Example 112D) in anhydrous dichloromethane (20 mL) and water (1.0 mL) was treated with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (224 mg, 0.986 mmol) and stirred for 20 minutes at ambient temperature. Additional 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (50 mg, 0.220 mmol) was added to the mixture, and the reaction stirred one hour at ambient temperature. The reaction was quenched with saturated sodium bicarbonate, and layers were separated. The organic layer was washed with brine, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by flash chromatography on silica gel, eluting with a gradient of 100% ethyl acetate to 5% methanol in ethyl acetate, to provide the title compound. MS ESI(+) m/z 539.1 [M+H]+.

Workup

  1. stirringthe reaction stirred one hour at ambient temperature
  2. customThe reaction was quenched with saturated sodium bicarbonate, and layers
  3. customwere separated
  4. washThe organic layer was washed with brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified by flash chromatography on silica gel
  9. washeluting with a gradient of 100% ethyl acetate to 5% methanol in ethyl acetate

Sources & evidence

ORD record
ord-fa3c01d2019e49c8b03d6b3383f722ce
Source dataset
uspto-grants-2014_04
Patent number
US08691810B2

Reaction notes

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