Triethylamine → Tert-butyl (1-(5-aminopyridin-2-yl)pyrrolidin-3-yl)(methyl)carbamate

HRID 526168Notes

Reaction equation

HRID 526168 reaction equation
[CH3:1][N:2]([CH:10]1[CH2:14][CH2:13][NH:12][CH2:11]1)[C:3](=[O:9])[O:4][C:5]([CH3:8])([CH3:7])[CH3:6].C(N(CC)CC)C.Cl[C:23]1[CH:28]=[CH:27][C:26]([N+:29]([O-])=O)=[CH:25][N:24]=1>C1COCC1>[NH2:29][C:26]1[CH:27]=[CH:28][C:23]([N:12]2[CH2:13][CH2:14][CH:10]([N:2]([CH3:1])[C:3](=[O:9])[O:4][C:5]([CH3:8])([CH3:6])[CH3:7])[CH2:11]2)=[N:24][CH:25]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 783082-Chloro-5-nitropyridineHCID 27614043-(N-tert-Butoxycarbonyl-N-methylamino)pyrrolidine

Product 1

HCID 57652013Tert-butyl (1-(5-aminopyridin-2-yl)pyrrolidin-3-yl)(methyl)carbamateYield 110.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of commercially available tert-butyl methyl(pyrrolidin-3-yl)carbamate (1.0 g, 5.0 mmol) in THF (25 mL) was added triethylamine (0.70 mL, 5.0 mmol) and 2-chloro-5-nitropyridine (500 mg, 3.1 mmol) and the reaction mixture was stirred at room temperature for 16 h. The reaction mixture was diluted with a satd. aq. NaHCO3 and extracted with ethyl acetate. The organic layer was dried over sodium sulfate, filtered and the filtrate was concentrated. The residue was purified by chromatography (silica, ethyl acetate/hexanes) to afford the desired product (1.0 g, quant.) as a yellow solid. The solid was dissolved in tetrahydrofuran (50 mL), degassed with nitrogen, charged with catalytic 10 wt. % Pd/C (0.5 g) and the reaction mixture was placed under an atmosphere of hydrogen (1 atm) until the reduction was complete by LCMS analysis. The reaction mixture was filtered over diatomaceous earth and the filtrate was concentrated to provide the desired product (940 mg, 100%) as a red oil. ESI MS m/z 293 [C15H24N4O2+H]+

Workup

  1. additionThe reaction mixture was diluted with a satd
  2. extractionaq. NaHCO3 and extracted with ethyl acetate
  3. dry with materialThe organic layer was dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationthe filtrate was concentrated
  6. customThe residue was purified by chromatography (silica, ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-05d5b39c7392470aa22cc8f8ef01d31d
Source dataset
uspto-grants-2016_05
Patent number
US09345709B2

Reaction notes

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