Benzophenone imine → 1,1-Dimethylethyl 4-(5-amino-2-pyrimidinyl)-1-piperazinecarboxylate

HRID 1713812Notes

Reaction equation

HRID 1713812 reaction equation
Br[C:2]1[CH:3]=[N:4][C:5]([N:8]2[CH2:13][CH2:12][N:11]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:10][CH2:9]2)=[N:6][CH:7]=1.CC(C)([O-])C.[Na+].C(=[NH:40])(C1C=CC=CC=1)C1C=CC=CC=1.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(=O)([O-])O.[Na+]>C1(C)C=CC=CC=1.CCOC(C)=O.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].C1COCC1>[NH2:40][C:2]1[CH:3]=[N:4][C:5]([N:8]2[CH2:13][CH2:12][N:11]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:10][CH2:9]2)=[N:6][CH:7]=1

Participants

10

Reactant 5

HCID 136809Benzophenone imineHCID 516892Sodium BicarbonateHCID 634876Binap, (A+-)-HCID 21914476tert-Butyl 4-(5-bromopyrimidin-2-yl)piperazine-1-carboxylateHCID 23676156Sodium t-butoxide

Product 1

HCID 594643191,1-Dimethylethyl 4-(5-amino-2-pyrimidinyl)-1-piperazinecarboxylateYield 92%

Reagents, catalysts & solvents 4

HCID 6505921(1E,4E)-1,5-diphenylpenta-1,4-dien-3-one; palladiumCatalystHCID 1140TolueneSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

Bis(dibenzylideneacetone)palladium (0.17 g, 0.29 mmol) was added to a mixture of tert-butyl 4-(5-bromopyrimidin-2-yl)piperazine-1-carboxylate (6.15 g, 17.92 mmol, prepared as described in Patent Application WO 2001087870), sodium tert-butoxide (2.41 g, 25.09 mmol), benzophenone imine (3.61 g, 21.50 mmol), and BINAP (0.34 g, 21.5 mmol) in anhydrous toluene (150 mL). The mixture was heated to 80° C. and stirred for 16 h under an atmosphere of nitrogen. The mixture was diluted with EtOAc (100 mL) and filtered through diatomaceous earth then concentrated by evaporation to give an oil. This intermediate was stirred together with THF (150 mL) and 2N 1HCl (100 mL) for 2 h. The mixture was then neutralised by the addition of saturated aqueous sodium hydrogen carbonate solution and the mixture was extracted with EtOAc (3×100 mL). The organic extracts were dried, filtered, concentrated by evaporation and triturated with hexane to give the title compound as a solid (4.6 g, 92%); 1H NMR δ: 7.90 (2H, s), 4.61 (2H, s), 3.51-3.45 (4H, m), 3.40-3.30 (4H, m), 1.20 (9H, s); MS m/e MH+: 280.

Workup

  1. filtrationfiltered through diatomaceous earth
  2. concentrationthen concentrated by evaporation
  3. customto give an oil
  4. extractionthe mixture was extracted with EtOAc (3×100 mL)
  5. customThe organic extracts were dried
  6. filtrationfiltered
  7. concentrationconcentrated by evaporation
  8. customtriturated with hexane

Sources & evidence

ORD record
ord-de3c376b81d24655a939a097b838119f
Source dataset
uspto-grants-2010_09
Patent number
US07795283B2

Reaction notes

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