Hydrochloric Acid → 2-chloromethyl-N-(4-methoxy-7-morpholin-4-yl-benzooxazol-2-yl)-isonicotinamide

HRID 1611964Notes

Reaction equation

HRID 1611964 reaction equation
[Cl:1][CH2:2][C:3]1[CH:4]=[C:5]([CH:9]=[CH:10][N:11]=1)[C:6]([OH:8])=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.[CH3:45][O:46][C:47]1[C:52]2[N:53]=[C:54]([NH2:56])[O:55][C:51]=2[C:50]([N:57]2[CH2:62][CH2:61][O:60][CH2:59][CH2:58]2)=[CH:49][CH:48]=1.Cl>C1COCC1.O1CCOCC1.CN(C=O)C.O>[Cl:1][CH2:2][C:3]1[CH:4]=[C:5]([CH:9]=[CH:10][N:11]=1)[C:6]([NH:56][C:54]1[O:55][C:51]2[C:50]([N:57]3[CH2:62][CH2:61][O:60][CH2:59][CH2:58]3)=[CH:49][CH:48]=[C:47]([O:46][CH3:45])[C:52]=2[N:53]=1)=[O:8]

Participants

10

Reactant 5

HCID 313Hydrochloric AcidHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 222522422-(Chloromethyl)isonicotinic acidHCID 22252247HCID 22252247, compound

Product 1

HCID 222522532-chloromethyl-N-(4-methoxy-7-morpholin-4-yl-benzooxazol-2-yl)-isonicotinamideYield 6.2%

Reagents, catalysts & solvents 4

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

Procedure

To a stirred solution of 72 mg (0.42 mmol) 2-choromethyl-isonicotinic acid in 5 ml THF were added 183 mg (0.48 mmol) HATU and 0.08 ml (0.48 mmol) N-ethyldiisopropylamine and stirring continued at room temperature for 5 h. A solution of 80 mg (0.32 mmol) 4-methoxy-7-morpholin-4-yl-benzooxazol-2-yl-amine in 5 ml dioxane and 1 ml DMF was then added and stirring continued at 40° C. for 48 h. The reaction mixture was then poured into 50 ml water, acidified with 1 M aq. hydrochloric acid, and extracted three times with ethyl acetate. The combined organic phases were dried over sodium sulfate and concentrated in vacuo. Flash chromatography (3/97 methanol/dichloromethane, then 10/90 methanol/dichloromethane) followed by trituration in ether afforded 8 mg (6%) 2-chloromethyl-N-(4-methoxy-7-morpholin-4-yl-benzooxazol-2-yl)-isonicotinamide as an off-white crystalline solid. ES-MS m/e (%): 405 (M{37Cl}+H+, 35), 403 (M{35Cl}+H+, 100).

Workup

  1. stirringstirring
  2. waitcontinued at 40° C. for 48 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-7dc4db4231d7439a91b8206957928123
Source dataset
uspto-grants-2006_01
Patent number
US06992083B2

Reaction notes

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