Water → tert-butyl (1S,3R)-3-(2-(5-tosyl-5H-pyrrolo[2,3-b]pyrazin-2-yl)hydrazinecarbonyl)cyclopentylcarbamate

HRID 2204528Notes

Reaction equation

HRID 2204528 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].[C:22]([O:26][C:27]([NH:29][C@H:30]1[CH2:34][CH2:33][C@@H:32]([C:35](O)=[O:36])[CH2:31]1)=[O:28])([CH3:25])([CH3:24])[CH3:23].CCN=C=NCCCN(C)C.Cl.O>C(Cl)Cl>[S:12]([N:9]1[C:6]2=[N:7][CH:8]=[C:3]([NH:1][NH:2][C:35]([C@@H:32]3[CH2:33][CH2:34][C@H:30]([NH:29][C:27](=[O:28])[O:26][C:22]([CH3:24])([CH3:23])[CH3:25])[CH2:31]3)=[O:36])[N:4]=[C:5]2[CH:11]=[CH:10]1)([C:15]1[CH:21]=[CH:20][C:18]([CH3:19])=[CH:17][CH:16]=1)(=[O:13])=[O:14]

Participants

6

Reactant 4

HCID 962WaterHCID 1512526(1R,3S)-3-[(2-methylpropan-2-yl)oxycarbonylamino]cyclopentane-1-carboxylic acidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 580098102-Hydrazinyl-5-tosyl-5H-pyrrolo[2,3-b]pyrazine

Product 1

HCID 58009789tert-butyl (1S,3R)-3-(2-(5-tosyl-5H-pyrrolo[2,3-b]pyrazin-2-yl)hydrazinecarbonyl)cyclopentylcarbamateYield 99.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To mixture of 2-hydrazinyl-5-tosyl-5H-pyrrolo[2,3-b]pyrazine (2.50 g, 8.24 mmol, Preparation #9) and (1R,3S)-3-(tert-butoxycarbonylamino)cyclopentanecarboxylic acid (2.08 g, 9.07 mmol, Peptech) in DCM (30 mL) was added EDC.HCl (1.90 g, 9.89 mmol). After about 4.5 h, water (30 mL) was added and the layers were separated. The aqueous layer was then extracted with EtOAc (15 mL). The combined organic layers were washed with brine, dried over anhydrous MgSO4, filtered, and concentrated under reduced pressure. The crude material was dissolved in DCM (15 mL) and purified by silica gel chromatography eluting with a gradient of 40-100% EtOAc in heptane to give tert-butyl (1S,3R)-3-(2-(5-tosyl-5H-pyrrolo[2,3-b]pyrazin-2-yl)hydrazinecarbonyl)cyclopentylcarbamate (4.20 g, 97%): LC/MS (Table 2, Method a) Rt=2.27 min; MS m/z: 515 (M+H)+.

Workup

  1. customthe layers were separated
  2. extractionThe aqueous layer was then extracted with EtOAc (15 mL)
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried over anhydrous MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. dissolutionThe crude material was dissolved in DCM (15 mL)
  8. custompurified by silica gel chromatography
  9. washeluting with a gradient of 40-100% EtOAc in heptane

Sources & evidence

ORD record
ord-e4a364e40dbd47349794243769357e52
Source dataset
uspto-grants-2016_06
Patent number
US09365579B2

Reaction notes

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