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 2362735노트

반응식

HRID 2362735 반응식
[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

참가 물질

6

반응물 3

HCID 6598Dimethylcarbamoyl Chloride2회HCID 8471Triethylamine2회HCID 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

생성물 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

시약·촉매·용매 2

HCID 962Water용매HCID 8028Tetrahydrofuran용매

반응 조건

온도
70 °C

실험 절차

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]+.

후처리

  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

출처 및 근거

ORD 기록
ord-e3f39731268f4bb6a24401c2be756b45
출처 데이터셋
uspto-grants-2014_04
특허 번호
US08691810B2

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