2-Amino-5-bromopyrazine → HCID 67517112, compound

HRID 1754330Notes

Reaction equation

HRID 1754330 reaction equation
Br[C:2]1[CH:3]=[C:4]([C:9]2[O:13][C:12](=[O:14])[N:11]([CH3:15])[N:10]=2)[CH:5]=[CH:6][C:7]=1[CH3:8].C[Sn](C)(C)[C:18]1[N:19]=[CH:20][C:21]([NH2:24])=[N:22][CH:23]=1.NC1C=NC(Br)=CN=1>C1COCC1.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>[NH2:24][C:21]1[N:22]=[CH:23][C:18]([C:2]2[CH:3]=[C:4]([C:9]3[O:13][C:12](=[O:14])[N:11]([CH3:15])[N:10]=3)[CH:5]=[CH:6][C:7]=2[CH3:8])=[N:19][CH:20]=1

Participants

6

Reactant 3

HCID 5995392-Amino-5-bromopyrazineHCID 59693786HCID 59693786, compoundHCID 67517243HCID 67517243, compound

Product 1

HCID 67517112HCID 67517112, compound

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
75 °C

Procedure

To a solution of 5-(3-bromo-4-methylphenyl)-3-methyl-1,3,4-oxadiazol-2(3H)-one (500 mg, 1.76 mmol) and 5-(trimethyl stannyl)-pyrazine-2-amine (683 mg, 2.65 mmol, prepared from 2-amino-5-bromopyrazine by following the procedure described in Chem. Eur. J. 2000, 6, 4132) in THF (10 mL) was added Pd(PPh3)4 (100 mg, 0.088 mmol). The resulting mixture was thoroughly deoxygenated by subjecting to vacuum/nitrogen cycle three times and the reaction mixture was heated at 75° C. for 15 h under nitrogen atmosphere. The resulting mixture was cooled to room temperature and filtered through celite. The filtrate was concentrated under vacuum and the crude product was purified by flash column chromatography over silica gel using ethyl acetate-hexane mixture as eluent to afford 250 mg of the intermediate 15b as a white solid. 1HNMR (400 MHz, DMSO-d6) δ 8.07 (s, 1H), 7.99 (s, 1H), 7.69 (d, J=2.0 Hz, 1H), 7.64 (dd, J=8.0, 2.0 Hz, 1H), 7.44 (d, J=8.0 Hz, 1H), 6.62 (s, 2H, D2O exchangeable), 3.36 (s, 3H), 2.35 (s, 3H); ESI-MS (m/z) 284 (MH)+.

Workup

  1. customThe resulting mixture was thoroughly deoxygenated
  2. temperatureThe resulting mixture was cooled to room temperature
  3. filtrationfiltered through celite
  4. concentrationThe filtrate was concentrated under vacuum
  5. customthe crude product was purified by flash column chromatography over silica gel

Sources & evidence

ORD record
ord-429a59a7c8384df599c3e20aba12a540
Source dataset
uspto-grants-2015_10
Patent number
US09169242B2

Reaction notes

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