Sodium hydride → 5-Bromo-3-cyclobutylmethoxy-2-pyrrolidin-1-yl-pyrazine

HRID 639299Notes

Reaction equation

HRID 639299 reaction equation
[H-].[Na+].[Br:3][C:4]1[N:5]=[C:6]([O:11][CH2:12][CH:13]2[CH2:16][CH2:15][CH2:14]2)[C:7]([NH2:10])=[N:8][CH:9]=1.Br[CH2:18][CH2:19][CH2:20][CH2:21]Cl>CN(C)C=O>[Br:3][C:4]1[N:5]=[C:6]([O:11][CH2:12][CH:13]2[CH2:14][CH2:15][CH2:16]2)[C:7]([N:10]2[CH2:21][CH2:20][CH2:19][CH2:18]2)=[N:8][CH:9]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 813641-Bromo-4-chlorobutaneHCID 866195175-Bromo-3-cyclobutylmethoxy-pyrazin-2-ylamine

Product 1

HCID 866195185-Bromo-3-cyclobutylmethoxy-2-pyrrolidin-1-yl-pyrazineYield 60%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Sodium hydride (0.98 g, 25.6 mmol) was added in portions to a solution of 5-bromo-3-cyclobutylmethoxy-pyrazin-2-ylamine (3.1 g, 12.2 mmol) in N,N-dimethylformamide (60 mL) under nitrogen at room temperature. After 20 minutes 1-bromo-4-chlorobutane (1.5 mL, 13.4 mmol) was added and the reaction mixture was stirred for 16 hours. The reaction mixture was poured onto ice and the whole was extracted with ethyl acetate (50 mL) and washed with water (30 mL×2), the organic layer was dried over MgSO4 and concentrated in vacuo. The crude product was purified by flash column chromatography (30% ethyl acetate/heptane) to afford 5-bromo-3-cyclobutylmethoxy-2-pyrrolidin-1-yl-pyrazine as a yellow solid 2.27 g (60% yield). LC@215 nm; Rt 2.72: 100%, m/z (ES+): 313 (M+H).

Workup

  1. additionThe reaction mixture was poured onto ice
  2. extractionthe whole was extracted with ethyl acetate (50 mL)
  3. washwashed with water (30 mL×2)
  4. dry with materialthe organic layer was dried over MgSO4
  5. concentrationconcentrated in vacuo
  6. customThe crude product was purified by flash column chromatography (30% ethyl acetate/heptane)

Sources & evidence

ORD record
ord-ec6bca7b4e9a4e938152c92174270bfb
Source dataset
uspto-grants-2010_04
Patent number
US07691863B2

Reaction notes

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