Diisopropylethylamine → Methyl 3-(3-(1-(2-(benzyloxy)phenyl)cyclobutylamino)-5-bromo-2-oxopyrazin-1(2H)-yl)-4-methylbenzoate

HRID 337104Notes

Reaction equation

HRID 337104 reaction equation
Br[C:2]1[C:3](=[O:20])[N:4]([C:9]2[CH:10]=[C:11]([CH:16]=[CH:17][C:18]=2[CH3:19])[C:12]([O:14][CH3:15])=[O:13])[CH:5]=[C:6]([Br:8])[N:7]=1.[CH2:21]([O:28][C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=1[C:35]1([NH2:39])[CH2:38][CH2:37][CH2:36]1)[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1.C(N(CC)C(C)C)(C)C>O1CCOCC1.C(OCC)(=O)C.O>[CH2:21]([O:28][C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=1[C:35]1([NH:39][C:2]2[C:3](=[O:20])[N:4]([C:9]3[CH:10]=[C:11]([CH:16]=[CH:17][C:18]=3[CH3:19])[C:12]([O:14][CH3:15])=[O:13])[CH:5]=[C:6]([Br:8])[N:7]=2)[CH2:38][CH2:37][CH2:36]1)[C:22]1[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=1

Participants

7

Reactant 3

HCID 81531DiisopropylethylamineHCID 66688740methyl 3-(3,5-dibromo-2-oxopyrazin-1(2H)-yl)-4-methylbenzoateHCID 666900331-[2-(Benzyloxy)phenyl]cyclobutan-1-amine

Product 1

HCID 66689709Methyl 3-(3-(1-(2-(benzyloxy)phenyl)cyclobutylamino)-5-bromo-2-oxopyrazin-1(2H)-yl)-4-methylbenzoateYield 94.3%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

To 3-(3,5-dibromo-2-oxo-2H-pyrazin-1-yl)-4-methyl-benzoic acid, methyl ester (Example 1b, 1.083 g) in dioxane (6 mL) was added 1-(2-(benzyloxy)phenyl)cyclobutanamine (Example 268c, 1.16 g) and N,N-diisopropylethylamine (0.76 mL) and the reaction heated at 100° C. for 16 h. After cooling to room temperature, the reaction mixture was diluted with ethyl acetate and water, and the organic layer was separated, dried (MgSO4), filtered and the crude product purified (SiO2 chromatography eluting with 20-50% ethyl acetate in iso-hexane) to afford the subtitle product (1.46 g).

Workup

  1. temperatureAfter cooling to room temperature
  2. customthe organic layer was separated
  3. dry with materialdried (MgSO4)
  4. filtrationfiltered
  5. customthe crude product purified
  6. wash(SiO2 chromatography eluting with 20-50% ethyl acetate in iso-hexane)

Sources & evidence

ORD record
ord-76fbeefd4d5942ce894e298a88d778d2
Source dataset
uspto-grants-2014_11
Patent number
US08889692B2

Reaction notes

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