Oxalyl chloride → N-(5-(1,1-dimethylethyl)-3-isoxazolyl)-6-((3-fluoro-6,7-bis(methoxy)-4-quinolinyl)oxy)-1-naphthalenecarboxamide

HRID 1925302Notes

Reaction equation

HRID 1925302 reaction equation
[F:1][C:2]1[CH:3]=[N:4][C:5]2[C:10]([C:11]=1[O:12][C:13]1[CH:14]=[C:15]3[C:20](=[CH:21][CH:22]=1)[C:19]([C:23](Cl)=[O:24])=[CH:18][CH:17]=[CH:16]3)=[CH:9][C:8]([O:26][CH3:27])=[C:7]([O:28][CH3:29])[CH:6]=2.FC1C=NC2C(C=1OC1C=C3C(=CC=1)C(C(O)=O)=CC=C3)=CC(OC)=C(OC)C=2.C(Cl)(=O)C(Cl)=O.[NH2:65][C:66]1[CH:70]=[C:69]([C:71]([CH3:74])([CH3:73])[CH3:72])[O:68][N:67]=1>N1C=CC=CC=1>[CH3:72][C:71]([C:69]1[O:68][N:67]=[C:66]([NH:65][C:23]([C:19]2[C:20]3[C:15](=[CH:14][C:13]([O:12][C:11]4[C:10]5[C:5](=[CH:6][C:7]([O:28][CH3:29])=[C:8]([O:26][CH3:27])[CH:9]=5)[N:4]=[CH:3][C:2]=4[F:1])=[CH:22][CH:21]=3)[CH:16]=[CH:17][CH:18]=2)=[O:24])[CH:70]=1)([CH3:74])[CH3:73]

Participants

6

Reactant 4

HCID 65578Oxalyl chlorideHCID 1714733-Isoxazolamine, 5-(1,1-dimethylethyl)-HCID 24822773HCID 24822773, compoundHCID 866086186-(3-Fluoro-6,7-dimethoxyquinolin-4-yloxy)-1-naphthoyl chloride

Product 1

HCID 57774568N-(5-(1,1-dimethylethyl)-3-isoxazolyl)-6-((3-fluoro-6,7-bis(methoxy)-4-quinolinyl)oxy)-1-naphthalenecarboxamide

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Conditions

Temperature
80 °C

Procedure

Pyridine (1.0 mL) was added to a mixture of 6-(3-fluoro-6,7-dimethoxyquinolin-4-yloxy)-1-naphthoyl chloride (prepared from 6-(3-fluoro-6,7-dimethoxyquinolin-4-yloxy)-1-naphthoic acid and oxalyl chloride by the procedure described in Example 273) (0.044 g, 0.107 mmol) and 3-amino-5-t-butylisoxazole (0.075 g, 0.535 mmol). The mixture stirred at 80° C. for 10 h and was then cooled to RT. The mixture was concentrated and the residue was purified by preparative thin layer chromatography on silica gel plates (eluting with 5% MeOH—CH2Cl2). Further purification via preparative thin layer chromatography on silica gel plates (eluting with 90:10:1 CH2Cl2:MeOHl:NH4OH) afforded N-(5-(1,1-dimethylethyl)-3-isoxazolyl)-6-((3-fluoro-6,7-bis(methoxy)-4-quinolinyl)oxy)-1-naphthalenecarboxamide as an off-white solid. MS (ESI, pos. ion) m/z: 516.0 (M+H). Mass Calc'd for C29H26FN3O5: 515.5

Workup

  1. temperaturewas then cooled to RT
  2. concentrationThe mixture was concentrated
  3. customthe residue was purified by preparative thin layer chromatography on silica gel plates (eluting with 5% MeOH—CH2Cl2)
  4. customFurther purification via preparative thin layer chromatography
  5. washon silica gel plates (eluting with 90:10:1 CH2Cl2:MeOHl:NH4OH)

Sources & evidence

ORD record
ord-d35fed5dfd0a4f9c9cfc25abd3b3dacd
Source dataset
uspto-grants-2012_05
Patent number
US08178557B2

Reaction notes

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