Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1) → 2-ethyl-4-(tetrahydro-2H-pyran-4-yloxy)-N'-(5-tosyl-5H-pyrrolo[2,3-b]pyrazin-2-yl)cyclopentanecarbohydrazide

HRID 1969808Notes

Reaction equation

HRID 1969808 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[CH2:28][CH:27]([O:29][CH:30]2[CH2:35][CH2:34][O:33][CH2:32][CH2:31]2)[CH2:26][CH:25]1[C:36](O)=[O:37])[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[CH2:28][CH:27]([O:29][CH:30]2[CH2:31][CH2:32][O:33][CH2:34][CH2:35]2)[CH2:26][CH:25]1[C:36]([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:37])[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 585577642-ethyl-4-(tetrahydro-2H-pyran-4-yloxy)cyclopentanecarboxylic acid

Product 1

HCID 585579512-ethyl-4-(tetrahydro-2H-pyran-4-yloxy)-N'-(5-tosyl-5H-pyrrolo[2,3-b]pyrazin-2-yl)cyclopentanecarbohydrazideYield 74.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 2-hydrazinyl-5-tosyl-5H-pyrrolo[2,3-b]pyrazine (0.233 g, 0.767 mmol, WO2009152133 Preparation #9) and 2-ethyl-4-(tetrahydro-2H-pyran-4-yloxy)cyclopentanecarboxylic acid (0.190 g, 0.767 mmol) in DCM (8.00 mL) was added HATU (0.350 g, 0.920 mmol, Novabiochem) and TEA (0.43 mL, 3.07 mmol). The resulting suspension was stirred at ambient temperature for about 4 h. The reaction was partitioned between DCM (50 mL) and water (25 mL) and the layers were separated. The organic layer was washed with water (2×25 mL) and brine (30 mL), dried over anhydrous MgSO4, filtered, and concd to give a brown residue. The crude material was purified by silica gel chromatography using a gradient of 1-10% MeOH in DCM to give 2-ethyl-4-(tetrahydro-2H-pyran-4-yloxy)-N′-(5-tosyl-5H-pyrrolo[2,3-b]pyrazin-2-yl)cyclopentanecarbohydrazide (0.300 g, 74%); LC/MS (Table 1, Method b) Rt=2.20 min; MS m/z: 528 (M+H)+.

Workup

  1. customThe reaction was partitioned between DCM (50 mL) and water (25 mL)
  2. customthe layers were separated
  3. washThe organic layer was washed with water (2×25 mL) and brine (30 mL)
  4. dry with materialdried over anhydrous MgSO4
  5. filtrationfiltered
  6. customconcd to give a brown residue
  7. customThe crude material was purified by silica gel chromatography

Sources & evidence

ORD record
ord-dc8434b47878488db922f12156050c9c
Source dataset
uspto-grants-2013_04
Patent number
US08426411B2

Reaction notes

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