Benzophenone imine → (2-Amino-pyridin-4-yl)-[3-tert-butyl-2-methoxy-5-(2-methoxy-pyridin-3-yl)-phenyl]-methanone

HRID 2390802Notes

Reaction equation

HRID 2390802 reaction equation
[C:1]([C:5]1[C:6]([O:28][CH3:29])=[C:7]([C:19]([C:21]2[CH:26]=[CH:25][N:24]=[C:23](Cl)[CH:22]=2)=[O:20])[CH:8]=[C:9]([C:11]2[C:12]([O:17][CH3:18])=[N:13][CH:14]=[CH:15][CH:16]=2)[CH:10]=1)([CH3:4])([CH3:3])[CH3:2].C(=[NH:43])(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.CC(C)([O-])C.[Na+]>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]>[NH2:43][C:23]1[CH:22]=[C:21]([C:19]([C:7]2[CH:8]=[C:9]([C:11]3[C:12]([O:17][CH3:18])=[N:13][CH:14]=[CH:15][CH:16]=3)[CH:10]=[C:5]([C:1]([CH3:3])([CH3:2])[CH3:4])[C:6]=2[O:28][CH3:29])=[O:20])[CH:26]=[CH:25][N:24]=1

Participants

6

Reactant 4

HCID 136809Benzophenone imineHCID 634876Binap, (A+-)-HCID 23676156Sodium t-butoxideHCID 86638337[3-Tert-butyl-2-methoxy-5-(2-methoxy-pyridin-3-yl)-phenyl]-(2-chloro-pyridin-4-yl)-methanone

Product 1

HCID 67069931(2-Amino-pyridin-4-yl)-[3-tert-butyl-2-methoxy-5-(2-methoxy-pyridin-3-yl)-phenyl]-methanone

Reagents, catalysts & solvents 1

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst

Conditions

Temperature
80 °C

Procedure

step 3—A flask containing 42 (106 mg, 0.259 mmol), benzophenone imine (0.070 mL, 0.417 mmol), Pd2(dba)3 (11.5 mg, 0.013 mmol), racemic BINAP (23.8 mg, 0.038 mmol), and sodium tert-butoxide (35 mg, 0.364 mmol) was purged with argon 3 times before toluene (5 mL) was added. The reaction was heated overnight at 80° C. then cooled to RT. The reaction mixture was diluted with EtOAc, filtered through CELITE, and the filtrate was concentrated. The residue was taken up in a mixture of MeOH (5 mL) and hydroxylamine (50% wt solution in water, 0.5 mL) and stirred overnight at RT before it was concentrated. The crude residue was purified by SiO2 chromatography eluting with an EtOAc/hexane gradient (25 to 75% EtOAc) to afford (2-amino-pyridin-4-yl)-[3-tert-butyl-2-methoxy-5-(2-methoxy-pyridin-3-yl)-phenyl]-methanone (44) as a pale yellow oil.

Workup

  1. customwas purged with argon 3 times before toluene (5 mL)
  2. additionwas added
  3. temperaturethen cooled to RT
  4. additionThe reaction mixture was diluted with EtOAc
  5. filtrationfiltered through CELITE
  6. concentrationthe filtrate was concentrated
  7. additionThe residue was taken up in a mixture of MeOH (5 mL) and hydroxylamine (50% wt solution in water, 0.5 mL)
  8. concentrationwas concentrated
  9. customThe crude residue was purified by SiO2 chromatography
  10. washeluting with an EtOAc/hexane gradient (25 to 75% EtOAc)

Sources & evidence

ORD record
ord-b4c9845cf3a0435faea072184ea876ce
Source dataset
uspto-grants-2012_09
Patent number
US08273773B2

Reaction notes

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