(1R,3R)-3-((tert-Butoxycarbonyl)amino)cyclopentanecarboxylic acid → tert-butyl (1R,3R)-3-(2-(5-tosyl-5H-pyrrolo[2,3-b]pyrazin-2-yl)hydrazinecarbonyl)cyclopentylcarbamate

HRID 1969706Notes

Reaction equation

HRID 1969706 reaction equation
[C:1]([O:5][C:6]([NH:8][C@@H:9]1[CH2:13][CH2:12][C@@H:11]([C:14]([OH:16])=O)[CH2:10]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[NH:17]([C:19]1[N:20]=[C:21]2[CH:27]=[CH:26][N:25]([S:28]([C:31]3[CH:37]=[CH:36][C:34]([CH3:35])=[CH:33][CH:32]=3)(=[O:30])=[O:29])[C:22]2=[N:23][CH:24]=1)[NH2:18].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>C(Cl)Cl>[S:28]([N:25]1[C:22]2=[N:23][CH:24]=[C:19]([NH:17][NH:18][C:14]([C@@H:11]3[CH2:12][CH2:13][C@@H:9]([NH:8][C:6](=[O:7])[O:5][C:1]([CH3:2])([CH3:3])[CH3:4])[CH2:10]3)=[O:16])[N:20]=[C:21]2[CH:27]=[CH:26]1)([C:31]1[CH:32]=[CH:33][C:34]([CH3:35])=[CH:36][CH:37]=1)(=[O:29])=[O:30]

Participants

5

Reactant 3

HCID 1512527(1R,3R)-3-((tert-Butoxycarbonyl)amino)cyclopentanecarboxylic acidHCID 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]pyrazine

Product 1

HCID 58557152tert-butyl (1R,3R)-3-(2-(5-tosyl-5H-pyrrolo[2,3-b]pyrazin-2-yl)hydrazinecarbonyl)cyclopentylcarbamateYield 100%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To (1R,3R)-3-(tert-butoxycarbonylamino)cyclopentanecarboxylic acid (2.25 g, 9.81 mmol, Acros) in DCM (98 mL) was added 2-hydrazinyl-5-tosyl-5H-pyrrolo[2,3-b]pyrazine (2.98 g, 9.81 mmol), HATU (3.73 g, 9.81 mmol) and TEA (5.5 mL, 39 mmol). The reaction mixture was stirred at ambient temperature for about 4 h then diluted with DCM (300 mL). The reaction mixture was washed with water (2×80 mL), saturated aqueous NaHCO3 (80 mL), dried over anhydrous MgSO4, filtered, and concd under reduced pressure. The residue was purified using silica gel chromatography (220 g) eluting with a gradient of 50-100% EtOAc in DCM give tert-butyl (1R,3R)-3-(2-(5-tosyl-5H-pyrrolo[2,3-b]pyrazin-2-yl)hydrazinecarbonyl)cyclopentylcarbamate (5.03 g, 100%) as a brown solid: LC/MS (Table 1, Method b) Rt=2.18 min; MS m/z: 513 (M−H)−

Workup

  1. washThe reaction mixture was washed with water (2×80 mL), saturated aqueous NaHCO3 (80 mL)
  2. dry with materialdried over anhydrous MgSO4
  3. filtrationfiltered
  4. customThe residue was purified
  5. washeluting with a gradient of 50-100% EtOAc in DCM

Sources & evidence

ORD record
ord-b00c8e2b24c047b3916cc45db0e8c87b
Source dataset
uspto-grants-2013_04
Patent number
US08426411B2

Reaction notes

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