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

HRID 2204876Notes

Reaction equation

HRID 2204876 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 prodcut 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-5d84e11a793e4791a180ffda54987020
Source dataset
uspto-grants-2016_06
Patent number
US09365557B2

Reaction notes

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