4,5-dichloro-2-(1-methyl-1H-pyrazol-4-yl)-1-tosyl-1H-pyrrolo[2,3-b]pyridine → 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

HRID 2362715Notes

Reaction equation

HRID 2362715 reaction equation
Cl[C:2]1[C:7]([Cl:8])=[CH:6][N:5]=[C:4]2[N:9]([S:18]([C:21]3[CH:27]=[CH:26][C:24]([CH3:25])=[CH:23][CH:22]=3)(=[O:20])=[O:19])[C:10]([C:12]3[CH:13]=[N:14][N:15]([CH3:17])[CH:16]=3)=[CH:11][C:3]=12.[CH3:28][O:29][C:30]1[CH:59]=[CH:58][C:33]([CH2:34][NH:35][C:36]2([C:40]3[S:41][C:42]([Sn](CCCC)(CCCC)CCCC)=[CH:43][N:44]=3)[CH2:39][CH2:38][CH2:37]2)=[CH:32][CH:31]=1>CN(C)C=O.C(OCC)(=O)C.O.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[Cl:8][C:7]1[C:2]([C:42]2[S:41][C:40]([C:36]3([NH:35][CH2:34][C:33]4[CH:32]=[CH:31][C:30]([O:29][CH3:28])=[CH:59][CH:58]=4)[CH2:39][CH2:38][CH2:37]3)=[N:44][CH:43]=2)=[C:3]2[CH:11]=[C:10]([C:12]3[CH:13]=[N:14][N:15]([CH3:17])[CH:16]=3)[N:9]([S:18]([C:21]3[CH:27]=[CH:26][C:24]([CH3:25])=[CH:23][CH:22]=3)(=[O:20])=[O:19])[C:4]2=[N:5][CH:6]=1

Participants

7

Reactant 2

HCID 670029234,5-dichloro-2-(1-methyl-1H-pyrazol-4-yl)-1-tosyl-1H-pyrrolo[2,3-b]pyridineHCID 67003559N-(4-methoxybenzyl)-1-(5-(tributylstannyl)thiazol-2-yl)cyclobutanamine

Product 1

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

Reagents, catalysts & solvents 4

HCID 178418476HCID 178418476, compoundCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

A solution of 4,5-dichloro-2-(1-methyl-1H-pyrazol-4-yl)-1-tosyl-1H-pyrrolo[2,3-b]pyridine (Example 113C) (1.3 g, 3.09 mmol) and N-(4-methoxybenzyl)-1-(5-(tributylstannyl)thiazol-2-yl)cyclobutanamine (Example 112C) (2.45 g, 4.35 mmol) in anhydrous N,N-dimethylformamide (10 mL) was degassed for about 15 minutes under nitrogen. Bis(triphenylphosphine)palladium(II) dichloride (0.108 g, 0.154 mmol) was added to the degassed solution, and reaction was put under nitrogen, sealed, and heated to 100° C. for 16 hours. The reaction was cooled and diluted with ethyl acetate and water. The layers were separated, and organic layer was washed with water and brine, dried over anhydrous sodium sulfate, filtered, and concentrated. The residue was purified by flash chromatography on silica gel, eluting with a gradient of 40% to 50% ethyl acetate in hexanes, to provide the title compound. MS ESI(+) m/z 659.1 [M+H]+.

Workup

  1. customsealed
  2. temperatureThe reaction was cooled
  3. customThe layers were separated
  4. washorganic layer was washed with water and brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was purified by flash chromatography on silica gel
  9. washeluting with a gradient of 40% to 50% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-458ce8e2856b43ba93022f1ed43921cf
Source dataset
uspto-grants-2014_04
Patent number
US08691810B2

Reaction notes

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