1-Boc-3-aminopyrrolidine → 5-[3-amino-6-(4-isopropylsulfonylphenyl)pyrazin-2-yl]-N-pyrrolidin-3-yl-1,3,4-oxadiazole-2-carboxamide

HRID 78657Notes

Reaction equation

HRID 78657 reaction equation
[NH2:1][C:2]1[C:3]([C:20]2[O:24][C:23]([C:25](OCC)=[O:26])=[N:22][N:21]=2)=[N:4][C:5]([C:8]2[CH:13]=[CH:12][C:11]([S:14]([CH:17]([CH3:19])[CH3:18])(=[O:16])=[O:15])=[CH:10][CH:9]=2)=[CH:6][N:7]=1.[NH2:30][CH:31]1[CH2:35][CH2:34][N:33](C(OC(C)(C)C)=O)[CH2:32]1>C(O)C>[NH2:1][C:2]1[C:3]([C:20]2[O:24][C:23]([C:25]([NH:30][CH:31]3[CH2:35][CH2:34][NH:33][CH2:32]3)=[O:26])=[N:22][N:21]=2)=[N:4][C:5]([C:8]2[CH:13]=[CH:12][C:11]([S:14]([CH:17]([CH3:19])[CH3:18])(=[O:15])=[O:16])=[CH:10][CH:9]=2)=[CH:6][N:7]=1

Participants

4

Reactant 2

HCID 27563701-Boc-3-aminopyrrolidineHCID 59472382Ethyl 5-(3-amino-6-(4-(isopropylsulfonyl)phenyl)pyrazin-2-yl)-1,3,4-oxadiazole-2-carboxylate

Product 1

HCID 594716495-[3-amino-6-(4-isopropylsulfonylphenyl)pyrazin-2-yl]-N-pyrrolidin-3-yl-1,3,4-oxadiazole-2-carboxamideYield 41%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To a suspension of ethyl 5-[3-amino-6-(4-isopropylsulfonylphenyl)pyrazin-2-yl]-1,3,4-oxadiazole-2-carboxylate (100 mg, 0.34 mmol) in ethanol (2 mL), tert-butyl 3-aminopyrrolidine-1-carboxylate (49.1 mg, 0.26 mmol) was added and the resulting mixture heated under reflux overnight. The reaction mixture was cooled to room temperature and evaporated to dryness. The residue was taken up in CH2Cl2 (2.0 mL) and TFA (400 μL) was added and the reaction mixture stirred overnight at room temperature. The reaction mixture was passed through a bicarbonate cartridge and the filtrate concentrated in vacuo. The residue was passed through a TsOH cartridge eluting the product with 2M Ammonia in methanol (5 mL). The solid was triturated form acetonitrile to give the product as a yellow solid (44.94 mg, 41%); 1H NMR (400.0 MHz, DMSO) d 1.19 (d, 6H), 1.75 (s, 1H), 2.00 (d, 1H), 2.73-2.78 (m, 2H), 2.94 (s, 1H), 2.95 (dd, 1H), 3.47 (t, 1H), 4.40 (br s, 1H), 7.85 (br s, 2H), 7.98 (d, 2H), 8.32-8.34 (m, 2H), 9.09 (s, 1H) and 9.46 (d, 1H) ppm; MS (ES+) 458.22

Workup

  1. additionwas added
  2. temperaturethe resulting mixture heated
  3. temperatureunder reflux overnight
  4. customevaporated to dryness
  5. additionTFA (400 μL) was added
  6. concentrationthe filtrate concentrated in vacuo
  7. washeluting the product with 2M Ammonia in methanol (5 mL)
  8. customThe solid was triturated form acetonitrile

Sources & evidence

ORD record
ord-421875fc964f41e49b0a3215c3cf5d8d
Source dataset
uspto-grants-2014_09
Patent number
US08841308B2

Reaction notes

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