Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1) → N,N-diethyl-1-(3-ethyl-4-(2-(5-tosyl-5H-pyrrolo[2,3-b]pyrazin-2-yl)hydrazinecarbonyl)cyclopentyl)methanesulfonamide

HRID 1969702Notes

Reaction equation

HRID 1969702 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]([N:24]([CH2:39][CH3:40])[S:25]([CH2:28][CH:29]1[CH2:33][CH:32]([C:34](O)=[O:35])[CH:31]([CH2:37][CH3:38])[CH2:30]1)(=[O:27])=[O:26])[CH3:23].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>C(Cl)Cl>[CH2:39]([N:24]([CH2:22][CH3:23])[S:25]([CH2:28][CH:29]1[CH2:33][CH:32]([C:34]([NH:2][NH:1][C:3]2[N:4]=[C:5]3[CH:11]=[CH:10][N:9]([S:12]([C:15]4[CH:21]=[CH:20][C:18]([CH3:19])=[CH:17][CH:16]=4)(=[O:13])=[O:14])[C:6]3=[N:7][CH:8]=2)=[O:35])[CH:31]([CH2:37][CH3:38])[CH2:30]1)(=[O:27])=[O:26])[CH3:40]

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 585578104-((N,N-diethylsulfamoyl)methyl)-2-ethylcyclopentanecarboxylic acid

Product 1

HCID 58557160N,N-diethyl-1-(3-ethyl-4-(2-(5-tosyl-5H-pyrrolo[2,3-b]pyrazin-2-yl)hydrazinecarbonyl)cyclopentyl)methanesulfonamideYield 98.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a suspension of 2-hydrazinyl-5-tosyl-5H-pyrrolo[2,3-b]pyrazine (0.390 g, 1.287 mmol, Example #1 Step D), 4-((N,N-diethylsulfamoyl)methyl)-2-ethylcyclopentanecarboxylic acid (0.375 g, 1.287 mmol), and HATU (0.538 g, 1.416 mmol) in DCM (6.4 mL) was added TEA (0.538 mL, 3.86 mmol). The reaction mixture was stirred at ambient temperature for about 1 h. The reaction mixture was partitioned between water (50 mL) and DCM (50 mL). The aqueous layer was extracted with DCM (2×50 mL). The organic layers were combined and concd under reduced pressure. The material was purified by silica gel (120 g) chromatography eluting with a gradient of 20-100% EtOAc in DCM to provide N,N-diethyl-1-(3-ethyl-4-(2-(5-tosyl-5H-pyrrolo[2,3-b]pyrazin-2-yl)hydrazinecarbonyl)cyclopentyl)methanesulfonamide (0.730 g, 98%) as a brown solid: LC/MS (Table 1, Method b) Rt=2.39 min; MS m/z: 577 (M+H)+.

Workup

  1. customThe reaction mixture was partitioned between water (50 mL) and DCM (50 mL)
  2. extractionThe aqueous layer was extracted with DCM (2×50 mL)
  3. customThe material was purified by silica gel (120 g) chromatography
  4. washeluting with a gradient of 20-100% EtOAc in DCM

Sources & evidence

ORD record
ord-8f82224280bb4dd0818c7a53b32b2733
Source dataset
uspto-grants-2013_04
Patent number
US08426411B2

Reaction notes

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