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 1969882Notes

Reaction equation

HRID 1969882 reaction equation
[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]

Participants

5

Reactant 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

Product 1

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

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

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 silica gel chromatography eluting with a gradient of: 0-10% MeOH in DCM. 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)+.

Workup

  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 silica gel chromatography
  6. washeluting with a gradient of: 0-10% MeOH in DCM
  7. additionThe product containing fractions

Sources & evidence

ORD record
ord-1a29816ee89d4417a7d8e42d9df06cb5
Source dataset
uspto-grants-2013_04
Patent number
US08426411B2

Reaction notes

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