Benzophenone imine → tert-Butyl 4-(2-aminoisonicotinoyl)piperazine-1-carboxylate

HRID 1355481Notes

Reaction equation

HRID 1355481 reaction equation
Cl[C:2]1[CH:3]=[C:4]([CH:20]=[CH:21][N:22]=1)[C:5]([N:7]1[CH2:12][CH2:11][N:10]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH2:9][CH2:8]1)=[O:6].CC([O-])(C)C.[Na+].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1.C(=[NH:88])(C1C=CC=CC=1)C1C=CC=CC=1.Cl.C1COCC1.C([O-])(O)=O.[Na+]>C1(C)C=CC=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[NH2:88][C:2]1[CH:3]=[C:4]([CH:20]=[CH:21][N:22]=1)[C:5]([N:7]1[CH2:12][CH2:11][N:10]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH2:9][CH2:8]1)=[O:6]

Participants

9

Reactant 6

HCID 136809Benzophenone imineHCID 516892Sodium BicarbonateHCID 634876Binap, (A+-)-HCID 2774091tert-butyl 4-(2-chloroisonicotinoyl)tetrahydro-1(2H)-pyrazinecarboxylateHCID 18422008HCl tetrahydrofuranHCID 23676156Sodium t-butoxide

Product 1

HCID 18506804tert-Butyl 4-(2-aminoisonicotinoyl)piperazine-1-carboxylate

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of tert-butyl 4-(2-chloroisonicotinoyl)piperazine-1-carboxylate (17-1, 524 mg) in dry toluene (10 mL) was added NaOtBu (216 mg, 2.25 mmole), racemic BINAP (150 mg, 0.24 mmole), Pd2(dba)3 (74 mg, 0.08 mmole), and benzophenone imine (0.32 mL, 1.93 mmole) then the mixture was heated to 80° C. After 18 hr the mixture was cooled to RT. A solution of 1N HCl:THF (1:1) was added and stirring continued. After 4 hr the mixture was neutralized with saturated NaHCO3 and extracted with EtOAc (3×). The combined organic layers were dried (MgSO4), filtered, and concentrated. Flash column chromatography (gradient, 50-100% EtOAc/hexanes then 0-10%MeOH/CH2Cl2) gave the titled compound as a yellow solid. 1H-NMR (500 MHz, CDCl3) δ8.12 (d, 1H, J=5.13 Hz), 6.58 (d, 1H, J=5.13 Hz), 6.47 (s, 1H), 4.55 (bs, 2H), 3.72-3.36 (m, 4H), 1.47 (s, 9H); MS (ES) (M+H)+307.

Workup

  1. temperatureAfter 18 hr the mixture was cooled to RT
  2. extractionextracted with EtOAc (3×)
  3. dry with materialThe combined organic layers were dried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-7203fe7848c04029a23075b5978f7d23
Source dataset
uspto-grants-2003_07
Patent number
US06586423B2

Reaction notes

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