Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1) → 8-ethyl-N'-(5-tosyl-5H-pyrrolo[2,3-b]pyrazin-2-yl)-1,4-dioxaspiro[4.4]nonane-7-carbohydrazide

HRID 1969551노트

반응식

HRID 1969551 반응식
[NH:1]([C:3]1[N:4]=[C:5]2[CH:11]=[CH:10][N:9]([S:12]([C:15]3[CH:21]=[CH:20][C:18]([CH3:19])=[CH:17][CH:16]=3)(=[O:14])=[O:13])[C:6]2=[N:7][CH:8]=1)[NH2:2].[CH2:22]([CH:24]1[CH2:32][C:27]2([O:31][CH2:30][CH2:29][O:28]2)[CH2:26][CH:25]1[C:33](O)=[O:34])[CH3:23].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>C(Cl)Cl>[CH2:22]([CH:24]1[CH2:32][C:27]2([O:28][CH2:29][CH2:30][O:31]2)[CH2:26][CH:25]1[C:33]([NH:2][NH:1][C:3]1[N:4]=[C:5]2[CH:11]=[CH:10][N:9]([S:12]([C:15]3[CH:21]=[CH:20][C:18]([CH3:19])=[CH:17][CH:16]=3)(=[O:13])=[O:14])[C:6]2=[N:7][CH:8]=1)=[O:34])[CH3:23]

참가 물질

5

반응물 3

HCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 580098102-Hydrazinyl-5-tosyl-5H-pyrrolo[2,3-b]pyrazineHCID 585573038-Ethyl-1,4-dioxaspiro[4,4]nonane-7-carboxylic acid

생성물 1

HCID 585573298-ethyl-N'-(5-tosyl-5H-pyrrolo[2,3-b]pyrazin-2-yl)-1,4-dioxaspiro[4.4]nonane-7-carbohydrazide수율 89%

시약·촉매·용매 1

HCID 6344Dichloromethane용매2회

실험 절차

A 50 mL round bottom flask was charged with 2-hydrazinyl-5-tosyl-5H-pyrrolo[2,3-b]pyrazine (0.350 g, 1.16 mmol, Example #1, Step D), 8-ethyl-1,4-dioxaspiro[4.4]nonane-7-carboxylic acid (0.250 g, 1.25 mmol), and DCM (6.0 mL). To the reaction mixture was added HATU (0.483 g, 1.27 mmol) and TEA (0.64 mL, 4.6 mmol) and the resulting yellow suspension was stirred at rt for about 3 h. To the reaction solution was added DCM (25 mL) and the solution was washed with water and brine (20 mL each). The organic layer was dried over anhydrous MgSO4, filtered, and concd under reduced pressure to give a brown oil. The crude product was purified by flash silica gel chromatography (25 g Silicycle column) eluting with a gradient of: 0-10% MeOH in DCM over 25 min. The product containing fractions were concd under reduced pressure to give 8-ethyl-N′-(5-tosyl-5H-pyrrolo[2,3-b]pyrazin-2-yl)-1,4-dioxaspiro[4.4]nonane-7-carbohydrazide as a foam (0.50 g, 89%): LC/MS (Table 1, Method c) Rt=1.49 min; MS m/z: 486 (M+H)+.

후처리

  1. washthe solution was washed with water and brine (20 mL each)
  2. dry with materialThe organic layer was dried over anhydrous MgSO4
  3. filtrationfiltered
  4. customconcd under reduced pressure to give a brown oil
  5. customThe crude product was purified by flash silica gel chromatography (25 g Silicycle column)
  6. washeluting with a gradient of: 0-10% MeOH in DCM over 25 min
  7. additionThe product containing fractions

출처 및 근거

ORD 기록
ord-f399c8f4172f497b9d941857ab14038c
출처 데이터셋
uspto-grants-2013_04
특허 번호
US08426411B2

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