Aminopyrazine → (2S,4S)-Benzyl 4-methoxy-2-(pyrazin-2-ylcarbamoyl)pyrrolidine-1-carboxylate

HRID 1961382Notes

Reaction equation

HRID 1961382 reaction equation
[NH2:1][C:2]1[CH:7]=[N:6][CH:5]=[CH:4][N:3]=1.C([Mg]Cl)(C)C.[CH3:13][O:14][C@@H:15]1[CH2:19][N:18]([C:20]([O:22][CH2:23][C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)=[O:21])[C@H:17]([C:30](OC)=[O:31])[CH2:16]1>C1COCC1>[CH3:13][O:14][C@@H:15]1[CH2:19][N:18]([C:20]([O:22][CH2:23][C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)=[O:21])[C@H:17]([C:30](=[O:31])[NH:1][C:2]2[CH:7]=[N:6][CH:5]=[CH:4][N:3]=2)[CH2:16]1

Participants

5

Reactant 3

HCID 78747AminopyrazineHCID 14036172(2S,4S)-1-Benzyl 2-methyl 4-methoxypyrrolidine-1,2-dicarboxylateHCID 178418918HCID 178418918, compound

Product 1

HCID 59436412(2S,4S)-Benzyl 4-methoxy-2-(pyrazin-2-ylcarbamoyl)pyrrolidine-1-carboxylateYield 85.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of aminopyrazine (535 mg, 5.63 mmol) in THF (15 mL) was added isopropylmagnesium chloride (2.0 M THF solution, 2.7 mL, 5.35 mmol) dropwise at 0° C. The resulting slurry was stirred at room temperature for 30 min. A solution of (2S,4S)-1-benzyl 2-methyl 4-methoxypyrrolidine-1,2-dicarboxylate (550 mg, 1.88 mmol) in THF (2 mL) was added to the slurry. The reaction mixture was stirred at room temperature for 4 h and quenched with methanol (3 mL). The crude product was purified by preparative HPLC to give (2S,4S)-benzyl 4-methoxy-2-(pyrazin-2-ylcarbamoyl)pyrrolidine-1-carboxylate 18C (570 mg, 85%) as an oil. LC/MS [M+H]+: 356; Ret time (Method F): 2.32 min.

Workup

  1. stirringThe reaction mixture was stirred at room temperature for 4 h
  2. customquenched with methanol (3 mL)
  3. customThe crude product was purified by preparative HPLC

Sources & evidence

ORD record
ord-7ec2fd0e773d4157a70ca75a200d8778
Source dataset
uspto-grants-2013_04
Patent number
US08415340B2

Reaction notes

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