Benzophenone imine → 6-amino-N-(4-tert-butylbenzyl)-2-methyl-1,8-naphthyridine-3-carboxamide

HRID 1961474Notes

Reaction equation

HRID 1961474 reaction equation
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.Br[C:48]1[CH:49]=[C:50]2[C:55](=[N:56][CH:57]=1)[N:54]=[C:53]([CH3:58])[C:52]([C:59]([NH:61][CH2:62][C:63]1[CH:68]=[CH:67][C:66]([C:69]([CH3:72])([CH3:71])[CH3:70])=[CH:65][CH:64]=1)=[O:60])=[CH:51]2.C1(C(C2C=CC=CC=2)=[NH:80])C=CC=CC=1.CC([O-])(C)C.[K+]>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.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[NH2:80][C:48]1[CH:49]=[C:50]2[C:55](=[N:56][CH:57]=1)[N:54]=[C:53]([CH3:58])[C:52]([C:59]([NH:61][CH2:62][C:63]1[CH:68]=[CH:67][C:66]([C:69]([CH3:72])([CH3:71])[CH3:70])=[CH:65][CH:64]=1)=[O:60])=[CH:51]2

Participants

8

Reactant 4

HCID 136809Benzophenone imineHCID 634876Binap, (A+-)-HCID 23665647Potassium tert-butoxideHCID 667460516-bromo-N-(4-tert-butylbenzyl)-2-methyl-1,8-naphthyridine-3-carboxamide

Product 1

HCID 667461896-amino-N-(4-tert-butylbenzyl)-2-methyl-1,8-naphthyridine-3-carboxamideYield 2.6%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

9.2 mg (0.01 mmol) Pd2 dba3 and 19 mg (0.03 mmol) BINAP were added to a degassed mixture of 205 mg (0.5 mmol) 6-bromo-N-(4-tert-butylbenzyl)-2-methyl-1,8-naphthyridine-3-carboxamide, 100 ml (0.6 mmol) diphenylmethanimine and 79 mg (0.7 mmol) KOtBu in 2 ml toluene. The flask was sealed with a septa and heated at 80° C. over night. The reaction mixture was diluted with EtOAc and filtered through celite and SiO2 with EtOAc. The filtrate was concentrated and treated with THF and 1.0 M HCl for 2 h. The solution was diluted with 0.5 M Hcl and washed with EtOAc/Pet. ether 1:1. The aqueous phase was neutralized with 1 M NaOH and extracted twice with CH2Cl2. The organic phase was dried (MgSO4) and concentrated. Flash chromatography (CH2Cl2/MeOH 10:1) gave 4.6 mg of the title compound.

Workup

  1. customThe flask was sealed with a septa
  2. filtrationfiltered through celite and SiO2 with EtOAc
  3. concentrationThe filtrate was concentrated
  4. additiontreated with THF and 1.0 M HCl for 2 h
  5. additionThe solution was diluted with 0.5 M Hcl
  6. washwashed with EtOAc/Pet. ether 1:1
  7. extractionextracted twice with CH2Cl2
  8. dry with materialThe organic phase was dried (MgSO4)
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-9b2580aa1a2a4640bf93377ffff9fd41
Source dataset
uspto-grants-2013_04
Patent number
US08415333B2

Reaction notes

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