Dimethyl Sulfoxide → Ethyl 2-(5-bromo-3-((tetrahydro-2H-pyran-4-yl)methylamino)pyrazin-2-ylamino)acetate

HRID 717117Notes

Reaction equation

HRID 717117 reaction equation
Br[C:2]1[C:3]([NH:9][CH2:10][C:11]([O:13][CH2:14][CH3:15])=[O:12])=[N:4][CH:5]=[C:6]([Br:8])[N:7]=1.[O:16]1[CH2:21][CH2:20][CH:19]([CH2:22][NH2:23])[CH2:18][CH2:17]1.C(N(CC)C(C)C)(C)C.CS(C)=O>CO>[Br:8][C:6]1[N:7]=[C:2]([NH:23][CH2:22][CH:19]2[CH2:20][CH2:21][O:16][CH2:17][CH2:18]2)[C:3]([NH:9][CH2:10][C:11]([O:13][CH2:14][CH3:15])=[O:12])=[N:4][CH:5]=1

Participants

6

Reactant 4

HCID 679Dimethyl SulfoxideHCID 81531DiisopropylethylamineHCID 27732104-AminomethyltetrahydropyranHCID 57550751Ethyl 2-(3,5-dibromopyrazin-2-ylamino)acetate

Product 1

HCID 86644641Ethyl 2-(5-bromo-3-((tetrahydro-2H-pyran-4-yl)methylamino)pyrazin-2-ylamino)acetateYield 71.7%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
150 °C

Procedure

Ethyl 2-(3,5-dibromopyrazin-2-ylamino)acetate (2.00 g, 5.90 mmol), (tetrahydro-2H-pyran-4-yl)methanamine (0.713 g, 6.19 mmol), N,N-diisopropylethylamine (3.08 mL, 17.70 mmol) and dimethylsulfoxide (4 mL) were combined in a microwave vial with a stirbar and heated in a Biotage Emrys Optimizer microwave reactor at 150° C. for 1 h. The resulting mixture was transferred to a round bottom flask with methanol. The methanol and N,N-diisopropylethylamine were removed under reduced pressure and the residue purified using Biotage flash chromatography (5-100% ethyl acetate in hexane). Fractions containing the desired product were combined in a separatory funnel and washed twice with water and once with brine. The organics were dried over magnesium sulfate, filtered and concentrated under reduced pressure. The residue was dried under high vacuum at 50° C. to give impure desired product (1.578 g) as an amber waxy solid which was taken on to the next step without further purification. MS (ESI) m/z 373.4 [M]+, 375.4 [M+2]+.

Workup

  1. customThe methanol and N,N-diisopropylethylamine were removed under reduced pressure
  2. customthe residue purified
  3. additionFractions containing the desired product
  4. customwere combined in a separatory funnel
  5. washwashed twice with water and once with brine
  6. dry with materialThe organics were dried over magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe residue was dried under high vacuum at 50° C.

Sources & evidence

ORD record
ord-a5a6ba67cf4a4effb6afb7c597c8de1f
Source dataset
uspto-grants-2015_11
Patent number
US09193692B2

Reaction notes

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