4-Methylmorpholine → 5-(4-Chloro-phenyl)-6-(2,2,2-trifluoro-ethoxy)-pyridazine-3-carboxylic acid (5-cyclopropyl-[1,2,4]oxadiazol-3-ylmethyl)-amide

HRID 1528444Notes

Reaction equation

HRID 1528444 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:9]=[C:10]([C:20](O)=[O:21])[N:11]=[N:12][C:13]=2[O:14][CH2:15][C:16]([F:19])([F:18])[F:17])=[CH:4][CH:3]=1.CN1CCOCC1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.Cl.[CH:55]1([C:58]2[O:62][N:61]=[C:60]([CH2:63][NH2:64])[N:59]=2)[CH2:57][CH2:56]1>CN(C)C=O>[CH:55]1([C:58]2[O:62][N:61]=[C:60]([CH2:63][NH:64][C:20]([C:10]3[N:11]=[N:12][C:13]([O:14][CH2:15][C:16]([F:17])([F:18])[F:19])=[C:8]([C:5]4[CH:4]=[CH:3][C:2]([Cl:1])=[CH:7][CH:6]=4)[CH:9]=3)=[O:21])[N:59]=2)[CH2:57][CH2:56]1

Participants

6

Reactant 4

HCID 79724-MethylmorpholineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 56773494(5-Cyclopropyl-1,2,4-oxadiazol-3-yl)methanamine hydrochlorideHCID 66678582HCID 66678582, compound

Product 1

HCID 569286935-(4-Chloro-phenyl)-6-(2,2,2-trifluoro-ethoxy)-pyridazine-3-carboxylic acid (5-cyclopropyl-[1,2,4]oxadiazol-3-ylmethyl)-amideYield 66.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of 5-(4-chloro-phenyl)-6-(2,2,2-trifluoro-ethoxy)-pyridazine-3-carboxylic acid (example M, 100 mg, 0.300 mmol) in dimethylformamide (4 mL, dried), was added 4-methylmorpholine (CAS No. 109-02-4, 0.09 mL 0.901 mmol), HBTU (CAS No. 94790-37-1, 171 mg, 0.450 mmol), 5-cyclopropyl-[1,2,4]oxadiazol-3-methanamine hydrochloride (Chembridge, MFCD09864586, 52 mg, 0.300 mmol) at rt and this mixture was stirred for 12 h at rt. Volatile were removed under reduced pressure and the residue was extracted with ethyl acetate. The combined organic layer was washed with aq. NaHCO3 soln, brine and concentrated to afford the crude residue which was purified by column chromatography (100-200 silica gel, elution with ethyl acetate/hexane). The title compound (91 mg, 66.0% yield) was obtained as a white solid; LC-MS (UV peak area/ESI) 96.8%, 454.6 (M+H)+.

Workup

  1. customVolatile were removed under reduced pressure
  2. extractionthe residue was extracted with ethyl acetate
  3. washThe combined organic layer was washed with aq. NaHCO3 soln
  4. concentrationbrine and concentrated
  5. customto afford the crude residue which
  6. customwas purified by column chromatography (100-200 silica gel, elution with ethyl acetate/hexane)

Sources & evidence

ORD record
ord-0da85fbeb6f34752badcdbe4f05f5c3e
Source dataset
uspto-grants-2015_07
Patent number
US09090599B2

Reaction notes

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