Dimethylcarbamoyl Chloride → 3-(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)-1,1-dimethylurea

HRID 2362735Notes

Reaction equation

HRID 2362735 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(N(CC)CC)C.[CH3:44][N:45]([CH3:49])[C:46](Cl)=[O:47]>O1CCCC1.O>[Cl:1][C:2]1[C:3]([C:27]2[S:31][C:30]([C:32]3([NH:36][C:46](=[O:47])[N:45]([CH3:49])[CH3:44])[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

6

Reactant 3

HCID 6598Dimethylcarbamoyl Chloride2×HCID 8471Triethylamine2×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 670037723-(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)-1,1-dimethylurea

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 triethylamine (0.014 ml, 0.104 mmol) and dimethylcarbamoyl chloride (8.18 μl, 0.089 mmol), and the reaction mixture was heated to 70° C. for 16 hours. Additional dimethylcarbamoyl chloride (4.09 μl, 0.044 mmol) and triethylamine (0.007 ml, 0.052 mmol) were added, and reaction solution heated for another 16 hours at 70° C. The reaction was cooled, diluted with water, and extracted with dichloromethane. The extracts were combined and concentrated under reduced pressure. The residue was purified by flash chromatography on silica gel, eluting with a gradient of 2 to 5% methanol in dichloromethane, to provide the title compound. MS ESI(+) m/z 610.3 [M+H]+.

Workup

  1. customreaction solution
  2. temperatureheated for another 16 hours at 70° C
  3. temperatureThe reaction was cooled
  4. extractionextracted with dichloromethane
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by flash chromatography on silica gel
  7. washeluting with a gradient of 2 to 5% methanol in dichloromethane

Sources & evidence

ORD record
ord-e3f39731268f4bb6a24401c2be756b45
Source dataset
uspto-grants-2014_04
Patent number
US08691810B2

Reaction notes

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