Dichloromethane → Phenylmethyl 4-{5-amino-6-[(methylamino)carbonyl]pyrazin-2-yl}benzoate

HRID 646686Notes

Reaction equation

HRID 646686 reaction equation
[NH2:1][C:2]1[C:3]([C:9]([NH:11][CH3:12])=[O:10])=[N:4][C:5](Br)=[CH:6][N:7]=1.[CH2:13]([O:20][C:21]([C:23]1[CH:28]=[CH:27][C:26](B(O)O)=[CH:25][CH:24]=1)=[O:22])[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.C(N(CC)CC)C.ClCCl>CN(C=O)C>[NH2:1][C:2]1[N:7]=[CH:6][C:5]([C:26]2[CH:27]=[CH:28][C:23]([C:21]([O:20][CH2:13][C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)=[O:22])=[CH:24][CH:25]=2)=[N:4][C:3]=1[C:9]([NH:11][CH3:12])=[O:10]

Participants

6

Reactant 4

HCID 6344DichloromethaneHCID 8471TriethylamineHCID 27732514-(Benzyloxycarbonyl)phenylboronic AcidHCID 151481213-Amino-6-bromo-N-methylpyrazine-2-carboxamide

Product 1

HCID 68650283Phenylmethyl 4-{5-amino-6-[(methylamino)carbonyl]pyrazin-2-yl}benzoateYield 59.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
85 °C

Procedure

To a stirred mixture of 3-amino-6-bromo-N-methyl-2-pyrazinecarboxamide (0.577 g, 2.5 mmol), 4-benzyloxycarbonylphenylboronic acid (0.768 g, 3.0 mmol), triethylamine (1.01 g, 10 mmol) in 10 mL of DMF was added [1,1′-bis(diphenylphosphino)-ferrocene]dichloropalladium(II) complex with dichloromethane (1:1), (20.4 mg, 0.025 mmol). The stirred mixture was warmed to 80-90° C. for 12 h and then concentrated on a rotary evaporator under reduced pressure. The residue was dissolved in 50 mL of EtOAc, washed with brine (30 mL). The organic layer was filtered through celite, and then dried over anhydrous sodium sulfate. Filtration, concentration and column chromatography on silica EtOAc) gave a solid (450 mg, 59.7% yield). 1H NMR (400 MHz; DMSO-d6): 8.91 (s, 1H); 8.84 (br s, 1H); 8.33 (d, 2H); 8.02 (d, 2H); 7.30-7.48 (m, 5H); 5.38 (s, 2H); 2.86 (s, 3M); MS (EI) for C20H15N4O3: 363 (MH+).

Workup

  1. concentrationconcentrated on a rotary evaporator under reduced pressure
  2. dissolutionThe residue was dissolved in 50 mL of EtOAc
  3. washwashed with brine (30 mL)
  4. filtrationThe organic layer was filtered through celite
  5. dry with materialdried over anhydrous sodium sulfate
  6. filtrationFiltration, concentration and column chromatography on silica EtOAc)

Sources & evidence

ORD record
ord-d326b60a4af646aa98e463b402cc2bcb
Source dataset
uspto-grants-2010_04
Patent number
US07704995B2

Reaction notes

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