5-Aminopyrazine-2-carbonitrile → Tert-butyl 4-((2-(5-cyanopyrazin-2-ylamino)-5-nitropyridin-4-yloxy)methyl)piperidine-1-carboxylate

HRID 384651Notes

Reaction equation

HRID 384651 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+].Br[C:17]1[CH:22]=[C:21]([O:23][CH2:24][CH:25]2[CH2:30][CH2:29][N:28]([C:31]([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:32])[CH2:27][CH2:26]2)[C:20]([N+:38]([O-:40])=[O:39])=[CH:19][N:18]=1>CN(C=O)C.C1(C)C=CC=CC=1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[C:8]([C:5]1[N:6]=[CH:7][C:2]([NH:1][C:17]2[CH:22]=[C:21]([O:23][CH2:24][CH:25]3[CH2:30][CH2:29][N:28]([C:31]([O:33][C:34]([CH3:35])([CH3:37])[CH3:36])=[O:32])[CH2:27][CH2:26]3)[C:20]([N+:38]([O-:40])=[O:39])=[CH:19][N:18]=2)=[N:3][CH:4]=1)#[N:9]

Participants

6

Reactant 3

HCID 139252945-Aminopyrazine-2-carbonitrileHCID 23676156Sodium t-butoxideHCID 59613339Tert-butyl 4-((2-bromo-5-nitropyridin-4-yloxy)methyl)piperidine-1-carboxylate

Product 1

HCID 59613322Tert-butyl 4-((2-(5-cyanopyrazin-2-ylamino)-5-nitropyridin-4-yloxy)methyl)piperidine-1-carboxylateYield 124.2%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 21735183Dimethylformamide tolueneSolvent

Procedure

Palladium (II) acetate (14.7 mg, 0.07 mmol) was added to (±)-2,2″-bis(diphenylphosphino)-1,1″-binaphthalene (123 mg, 0.2 mmol) in DMF-toluene (1:1, 5 mL) and the mixture was degassed for 10 minutes under a stream of nitrogen gas. 2-Amino-5-cyanopyrazine (95 mg, 0.79 mmol), sodium-t-butoxide (76 mg, 0.79 mmol) and tert-butyl 4-((2-bromo-5-nitropyridin-4-yloxy)methyl)piperidine-1-carboxylate (273 mg, 0.67 mmol) were added and the mixture was degassed for a further 5 minutes before stirring at room temperature for 2 hours. The mixture was partitioned between ethyl acetate and water and the aqueous phase was extracted with ethyl acetate. The combined organic layers were washed with water and brine, then dried (Na2SO4) and concentrated to give crude tert-butyl 4-((2-(5-cyanopyrazin-2-ylamino)-5-nitropyridin-4-yloxy)methyl)piperidine-1-carboxylate (379 mg) which was used without further purification.

Workup

  1. customthe mixture was degassed for 10 minutes under a stream of nitrogen gas
  2. customthe mixture was degassed for a further 5 minutes
  3. customThe mixture was partitioned between ethyl acetate and water
  4. extractionthe aqueous phase was extracted with ethyl acetate
  5. washThe combined organic layers were washed with water and brine
  6. dry with materialdried (Na2SO4)
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-009d5410a2e8467fab30316350098045
Source dataset
uspto-grants-2013_02
Patent number
US08367658B2

Reaction notes

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