Diisopropylethylamine → 2-bromo-N-[7-(4-fluoro-phenyl)-4-methoxy-benzooxazol-2-yl]-isonicotinamide

HRID 1611950Notes

Reaction equation

HRID 1611950 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][N:10]=1)[C:5]([OH:7])=O.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(C(C)C)C(C)C)C.[F:44][C:45]1[CH:50]=[CH:49][C:48]([C:51]2[C:59]3[O:58][C:57]([NH2:60])=[N:56][C:55]=3[C:54]([O:61][CH3:62])=[CH:53][CH:52]=2)=[CH:47][CH:46]=1>C1COCC1.O1CCOCC1.CN(C=O)C.O>[Br:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][N:10]=1)[C:5]([NH:60][C:57]1[O:58][C:59]2[C:51]([C:48]3[CH:49]=[CH:50][C:45]([F:44])=[CH:46][CH:47]=3)=[CH:52][CH:53]=[C:54]([O:61][CH3:62])[C:55]=2[N:56]=1)=[O:7]

Participants

9

Reactant 4

HCID 81531DiisopropylethylamineHCID 2227012-Bromoisonicotinic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 222522347-(4-Fluoro-phenyl)-4-methoxy-benzooxazol-2-ylamine

Product 1

HCID 222522612-bromo-N-[7-(4-fluoro-phenyl)-4-methoxy-benzooxazol-2-yl]-isonicotinamideYield 68.4%

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolventHCID 312751,4-DioxaneSolvent

Procedure

To a stirred solution of 203 mg (1.00 mmol) 2-bromo-isonicotinic acid in 5 ml THF were added 442 mg (1.16 mmol) HATU and 0.20 ml (1.16 mmol) N-ethyldiisopropylamine and stirring continued at room temperature for 5 h. A solution of 200 mg (0.77 mmol) 7-(4-fluoro-phenyl)-4-methoxy-benzooxazol-2-yl-amine in 5 ml dioxane and 1 ml DMF was then added and stirring continued at 40° C. for 16 h. The reaction mixture was then poured into 100 ml water and extracted three times with ethyl acetate. The combined organic phases were dried over sodium sulfate and concentrated in vacuo. Trituration in ether/ethyl acetate (4/1) afforded 233 mg (68%) 2-bromo-N-[7-(4-fluoro-phenyl)-4-methoxy-benzooxazol-2-yl]-isonicotinamide as an off-white crystalline solid. ES-MS m/e (%): 444 (M{81Br}+H+, 90), 442 (M{79Br}+H+, 100).

Workup

  1. stirringstirring
  2. waitcontinued at 40° C. for 16 h
  3. extractionextracted three times with ethyl acetate
  4. dry with materialThe combined organic phases were dried over sodium sulfate
  5. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-3b369e36438242c68728f8a891bce7d9
Source dataset
uspto-grants-2006_01
Patent number
US06992083B2

Reaction notes

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