Dichloromethane → HCID 68651564, compound

HRID 646665Notes

Reaction equation

HRID 646665 reaction equation
[NH2:1][C:2]1[C:3]([C:9]([O:11][CH3:12])=[O:10])=[N:4][C:5](Br)=[CH:6][N:7]=1.ClCCl.[C:16]1(B(O)O)[C:25]2[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=2)[CH:19]=[CH:18][CH:17]=1.C(N(CC)CC)C>CN(C)C=O>[NH2:1][C:2]1[C:3]([C:9]([O:11][CH3:12])=[O:10])=[N:4][C:5]([C:24]2[C:25]3[C:20](=[CH:19][CH:18]=[CH:17][CH:16]=3)[CH:21]=[CH:22][CH:23]=2)=[CH:6][N:7]=1

Participants

6

Reactant 4

HCID 6344DichloromethaneHCID 8471TriethylamineHCID 227251Methyl 3-Amino-6-bromopyrazine-2-carboxylateHCID 2545321-Naphthaleneboronic acid

Product 1

HCID 68651564HCID 68651564, compoundYield 39%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
87.5 °C

Procedure

To a solution of methyl 3-amino-6-bromopyrazine-2-carboxylate (0.18 g, 0.74 mmol) in N,N-dimethylformamide (10 mL) were added [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) complex with dichloromethane (1:1, 60 mg, 0.07 mmol), 1-naphthylboronic acid (0.32 g, 1.89 mmol), and triethylamine (0.15g, 1.52 mmol). The solution was degassed with nitrogen for 3-5 min. The reaction was then heated to 85-90° C. overnight. The reaction was cooled to room temperature and diluted with ethyl acetate (300 mL). The crude solution was passed through a pad of silica gel under vacuum. The filtrate was washed with saturated aqueous sodium bicarbonate (50 mL) and saturated aqueous sodium chloride (50 mL). The organic layer was dried over magnesium sulfate, filtered and concentrated at reduced pressure to afford impure product. Column purification on silica (8:2 hexanes/ethyl acetate) afforded methyl 3-amino-6-naphthalen-1-ylpyrazine-2-carboxylate (80 mg, 39% yield) as yellow solid: 1H NMR (400 MHz, CDCl3): δ 8.52 (br s, 1H), 8.12 (br s, 1H), 7.92 (m, 2H), 7.52 (m, 5H), 4.02 (s, 3H); MS (EI) for C16H13N3O2: 280 (MHz).

Workup

  1. customThe solution was degassed with nitrogen for 3-5 min
  2. temperatureThe reaction was cooled to room temperature
  3. additiondiluted with ethyl acetate (300 mL)
  4. washThe filtrate was washed with saturated aqueous sodium bicarbonate (50 mL) and saturated aqueous sodium chloride (50 mL)
  5. dry with materialThe organic layer was dried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated at reduced pressure
  8. customto afford impure product
  9. customColumn purification on silica (8:2 hexanes/ethyl acetate)

Sources & evidence

ORD record
ord-89c0caee324c44a8946b21656b986de2
Source dataset
uspto-grants-2010_04
Patent number
US07704995B2

Reaction notes

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