Sodium Carbonate → 3-(4-Aminophenyl)-5-[2-(4-morpholinyl)-4-pyridinyl]-2-pyrazinamine

HRID 1853095Notes

Reaction equation

HRID 1853095 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:9]([NH2:15])=[N:10][CH:11]=[C:12](Br)[N:13]=2)=[CH:4][CH:3]=1.CC1(C)C(C)(C)OB([C:24]2[CH:29]=[CH:28][N:27]=[C:26]([N:30]3[CH2:35][CH2:34][O:33][CH2:32][CH2:31]3)[CH:25]=2)O1.C([O-])([O-])=O.[Na+].[Na+]>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.O1CCOCC1.O>[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:9]([NH2:15])=[N:10][CH:11]=[C:12]([C:24]3[CH:29]=[CH:28][N:27]=[C:26]([N:30]4[CH2:31][CH2:32][O:33][CH2:34][CH2:35]4)[CH:25]=3)[N:13]=2)=[CH:4][CH:3]=1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 210816614-(4-(Tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl)morpholineHCID 867248623-(4-Aminophenyl)-5-bromo-2-pyrazinamine

Product 1

HCID 682888223-(4-Aminophenyl)-5-[2-(4-morpholinyl)-4-pyridinyl]-2-pyrazinamineYield 84.3%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 218864351,4-Dioxane--water (1/1)Solvent

Conditions

Temperature
90 °C

Procedure

A suspension of the compound prepared in Example 12 (7.6 g), Pd(PPh3)4 (3.3 g), 4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl)morpholine (8.3 g), and Na2CO3 (9.1 g, 85 mmol) in a 3 to 1 mixture of dioxane/water (280 mL) was degassed with a stream of nitrogen for 10 minutes. The reaction was heated at 90° C. overnight, at which time LC/MS indicated the reaction was complete. The mixture was concentrated, diluted with aqueous saturated sodium bicarbonate solution (200 mL) and extracted with EtOAc (3×200 mL). The organic layers were combined, dried over Na2SO4, and evaporated under reduced pressure. The crude product was obtained as a brown oil which was precipitated from DCM (50 mL) to give a dark yellow solid. The solid was filtered and triturated with a 1 to 1 solution of DCM/EtOAc (3×50 mL) to give the title compound (8.4 g) having the following physical data as a light yellow solid.

Workup

  1. customwas degassed with a stream of nitrogen for 10 minutes
  2. concentrationThe mixture was concentrated
  3. additiondiluted with aqueous saturated sodium bicarbonate solution (200 mL)
  4. extractionextracted with EtOAc (3×200 mL)
  5. dry with materialdried over Na2SO4
  6. customevaporated under reduced pressure
  7. customThe crude product was obtained as a brown oil which
  8. customwas precipitated from DCM (50 mL)
  9. customto give a dark yellow solid
  10. filtrationThe solid was filtered
  11. customtriturated with a 1 to 1 solution of DCM/EtOAc (3×50 mL)

Sources & evidence

ORD record
ord-d2f5227378f1428395f1532535103147
Source dataset
uspto-grants-2015_02
Patent number
US08962623B2

Reaction notes

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