5-Aminopyrazine-2-carbonitrile → 5-(1-(4-methoxybenzyl)-1H-imidazo[4,5-c]pyridin-6-ylamino)pyrazine-2-carbonitrile

HRID 40670

Reaction equation

HRID 40670 reaction equation
[NH2:1][C:2]1[CH:7]=[N:6][C:5]([C:8]#[N:9])=[CH:4][N:3]=1.CC(C)([O-])C.[Na+].[CH3:16][O:17][C:18]1[CH:34]=[CH:33][C:21]([CH2:22][N:23]2[C:31]3[CH:30]=[C:29](Br)[N:28]=[CH:27][C:26]=3[N:25]=[CH:24]2)=[CH:20][CH:19]=1>CN(C=O)C.C1(C)C=CC=CC=1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:16][O:17][C:18]1[CH:19]=[CH:20][C:21]([CH2:22][N:23]2[C:31]3[CH:30]=[C:29]([NH:1][C:2]4[N:3]=[CH:4][C:5]([C:8]#[N:9])=[N:6][CH:7]=4)[N:28]=[CH:27][C:26]=3[N:25]=[CH:24]2)=[CH:33][CH:34]=1

Participants

6

Reactant 3

HCID 139252945-Aminopyrazine-2-carbonitrileHCID 23676156Sodium t-butoxideHCID 569264661-(4-methoxybenzyl)-6-bromo-1H-imidazo[4,5-c]pyridine

Product 1

HCID 442043575-(1-(4-methoxybenzyl)-1H-imidazo[4,5-c]pyridin-6-ylamino)pyrazine-2-carbonitrileYield 40%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 21735183Dimethylformamide tolueneSolvent

Conditions

Temperature
150 °C

Procedure

Palladium (II) acetate (3.5 mg, 16 μmol) was added to (±)-2,2″-bis(diphenylphosphino)-1,1″-binaphthalene (59 mg, 94 μmol) in DMF/toluene (1:2) and the resulting mixture was degassed under a stream of nitrogen gas for 10 minutes. 2-Amino-5-cyanopyrazine (19 mg, 0.16 mmol), sodium tert-butoxide (45 mg, 0.47 mmol) and 1-(4-methoxybenzyl)-6-bromo-1H-imidazo[4,5-c]pyridine (50 mg, 0.16 mmol) were added and the mixture was degassed for a further 5 minutes before heating at 150° C. for 30 minutes using microwave irradiation. The reaction mixture was partitioned between water and dichloromethane. The aqueous phase extracted with dichloromethane. The combined organic layers were dried (Na2SO4) and concentrated. The residue was dissolved in methanol, passed through a PS-Thiol column and concentrated. The product was purified using preparative HPLC to give the title compound (22.4 mg, 40%). 1H NMR (d6-DMSO, 400 MHz) δ 10.84 (br s, 1H), 8.77 (d, 1H, J=1.3 Hz), 8.74 (m, 2H), 8.49 (s, 1H), 8.17 (s, 1H), 7.34 (m, 2H), 5.41 (s, 2H), 3.72 (s, 3H). LCMS (2) Rt=2.32 min; m/z (ESI+) 358 (MH+), (ESI−) 356 (M−H).

Workup

  1. customthe resulting mixture was degassed under a stream of nitrogen gas for 10 minutes
  2. customthe mixture was degassed for a further 5 minutes
  3. custommicrowave irradiation
  4. customThe reaction mixture was partitioned between water and dichloromethane
  5. extractionThe aqueous phase extracted with dichloromethane
  6. dry with materialThe combined organic layers were dried (Na2SO4)
  7. concentrationconcentrated
  8. dissolutionThe residue was dissolved in methanol
  9. concentrationconcentrated
  10. customThe product was purified

Sources & evidence

ORD record
ord-68a88dca70fb4c9daa1ea5cb4026c9b2
Source dataset
uspto-grants-2013_09
Patent number
US08530468B2

Linked notes

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