Trimethylsilyl isocyanate → 1-(1-(5-(5-chloro-2-(1-methyl-1H-pyrazol-4-yl)-1-tosyl-1H-pyrrolo[2,3-b]pyridin-4-yl)thiazol-2-yl)cyclobutyl)urea

HRID 2362734Notes

Reaction equation

HRID 2362734 reaction equation
[Cl:1][C:2]1[C:3]([C:27]2[S:31][C:30]([C:32]3([NH2:36])[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.C[Si]([N:41]=[C:42]=[O:43])(C)C>O1CCCC1.O>[Cl:1][C:2]1[C:3]([C:27]2[S:31][C:30]([C:32]3([NH:36][C:42]([NH2:41])=[O:43])[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 70696Trimethylsilyl isocyanate2×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

Product 1

HCID 670034511-(1-(5-(5-chloro-2-(1-methyl-1H-pyrazol-4-yl)-1-tosyl-1H-pyrrolo[2,3-b]pyridin-4-yl)thiazol-2-yl)cyclobutyl)urea

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
70 °C

Procedure

A mixture 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)cyclobutanamine (40 mg, 0.074 mmol) (Example 121A) in anhydrous tetrahydrofuran (1 mL) was treated with trimethylsilyl isocyanate (0.049 ml, 0.371 mmol), and the reaction mixture was heated to 70° C. for 5 hours. Additional trimethylsilyl isocyanate (0.025 ml, 0.185 mmol) was added, and the reaction solution was heated for 16 hours at 70° C. The reaction was cooled, diluted with water, and extracted with dichloromethane. The organic extracts were combined and concentrated under reduced pressure. The residue was purified by flash chromatography on silica gel, eluting with 5% methanol in dichloromethane, to provide the title compound. MS ESI(+) m/z 582.3 [M+H]+.

Workup

  1. temperaturethe reaction solution was heated for 16 hours at 70° C
  2. temperatureThe reaction was cooled
  3. extractionextracted with dichloromethane
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was purified by flash chromatography on silica gel
  6. washeluting with 5% methanol in dichloromethane

Sources & evidence

ORD record
ord-6bf54e86d8d341a39eb167b633b88812
Source dataset
uspto-grants-2014_04
Patent number
US08691810B2

Reaction notes

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