Diisopropylethylamine → 5-(5,6-dihydro-4H-pyran-2-yl)-pyrazin-2-ylamine

HRID 719997Notes

Reaction equation

HRID 719997 reaction equation
[NH2:1][C:2]1[CH:7]=[N:6][C:5](Br)=[CH:4][N:3]=1.C(N(CC)C(C)C)(C)C.[Cl-].[Li+].C([Sn](CCCC)(CCCC)[C:25]1[O:26][CH2:27][CH2:28][CH2:29][CH:30]=1)CCC.[F-].[K+]>CN(C)C=O.C(Cl)Cl.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[O:26]1[CH2:27][CH2:28][CH2:29][CH:30]=[C:25]1[C:5]1[N:6]=[CH:7][C:2]([NH2:1])=[N:3][CH:4]=1

Participants

9

Reactant 5

HCID 81531DiisopropylethylamineHCID 433294Lithium ChlorideHCID 522689Potassium FluorideHCID 5995392-Amino-5-bromopyrazineHCID 4216837tributyl(3,4-dihydro-2H-pyran-6-yl)stannane

Product 1

HCID 218973825-(5,6-dihydro-4H-pyran-2-yl)-pyrazin-2-ylamineYield 25%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
120 °C

Procedure

A solution of 2-amino-5-bromopyrazine (100 mg, 0.58 mmol) in N,N-dimethylformamide (6 mL) was treated with tetrakis(triphenylphosphine)palladium(0) (13 mg, 0.01 mmol), N,N-diisopropylethylamine (250 μL, 1.43 mmol), lithium chloride (85 mg, 2.01 mmol), and 5,6-dihydro-2-(tributylstannyl)-4H-pyran (214 mg, 0.58 mmol). The resulting reaction mixture was heated at 120° C. for 4 h. After such time, the reaction was cooled to 25° C., treated with a saturated aqueous potassium fluoride solution (10 mL), and stirred at 25° C. overnight for 16 h. The solution was then diluted with methylene chloride (25 mL) and extracted with methylene chloride (3×15 mL). The combined organic layers were dried over sodium sulfate, filtered, and concentrated in vacuo. Biotage chromatography (FLASH 12M, Silica, 1/1 to 1/3 hexanes/ethyl acetate) afforded 5-(5,6-dihydro-4H-pyran-2-yl)-pyrazin-2-ylamine (25 mg, 25%) as a foam: EI-HRMS m/e calcd for C9H11N3O (M+) 177.0902, found 177.0906.

Workup

  1. customThe resulting reaction mixture
  2. temperatureAfter such time, the reaction was cooled to 25° C.
  3. extractionextracted with methylene chloride (3×15 mL)
  4. dry with materialThe combined organic layers were dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-bc9aadd70dd346e0885f1e8a695a3553
Source dataset
uspto-grants-2006_11
Patent number
US07132425B2

Reaction notes

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