Acetic Anhydride → 1-[3-[2-(cyclopropylamino)-4-pyrimidinyl]-2-(4-fluorophenyl)-5,6-dihydropyrazolo[1,5-b]pyridazin-7(4H)-yl]ethanone

HRID 2063260Notes

Reaction equation

HRID 2063260 reaction equation
[CH:1]1([NH:4][C:5]2[N:10]=[C:9]([C:11]3[C:12]([C:20]4[CH:25]=[CH:24][C:23]([F:26])=[CH:22][CH:21]=4)=[N:13][N:14]4[C:19]=3[CH2:18][CH2:17][CH2:16][NH:15]4)[CH:8]=[CH:7][N:6]=2)[CH2:3][CH2:2]1.[C:27](OC(=O)C)(=[O:29])[CH3:28]>CN(C)C1C=CN=CC=1.N1C=CC=CC=1.O>[CH:1]1([NH:4][C:5]2[N:10]=[C:9]([C:11]3[C:12]([C:20]4[CH:21]=[CH:22][C:23]([F:26])=[CH:24][CH:25]=4)=[N:13][N:14]4[C:19]=3[CH2:18][CH2:17][CH2:16][N:15]4[C:27](=[O:29])[CH3:28])[CH:8]=[CH:7][N:6]=2)[CH2:3][CH2:2]1

Participants

6

Reactant 2

HCID 7918Acetic AnhydrideHCID 68514466N-cyclopropyl-4-[2-(4-fluorophenyl)-4,5,6,7-tetrahydropyrazolo[1,5-b]pyridazin-3-yl]-2-pyrimidinamine

Product 1

HCID 685137641-[3-[2-(cyclopropylamino)-4-pyrimidinyl]-2-(4-fluorophenyl)-5,6-dihydropyrazolo[1,5-b]pyridazin-7(4H)-yl]ethanone

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 962WaterSolventHCID 1049PyridineSolvent

Procedure

A catalytic amount of 4-dimethylaminopyridine (ca. 5 mg) was added to a solution of N-cyclopropyl-4-[2-(4-fluorophenyl)-4,5,6,7-tetrahydropyrazolo[1,5-b]pyridazin-3-yl]-2-pyrimidinamine (i.e. the product of Step E) (42.1 mg, 0.12 mmol) and acetic anhydride (0.023 mL, 0.24 mmol) in 2 mL of pyridine at room temperature. After 3 h the reaction mixture was diluted with water and extracted with ethyl acetate (3×10 mL). The combined organic phase was dried over magnesium sulfate, filtered and concentrated under reduced pressure. The crude residue was purified by medium pressure liquid chromatography using 20-100% ethyl acetate in hexanes as eluent to give 25 mg of the title product, a compound of the present invention, as a white solid.

Workup

  1. extractionextracted with ethyl acetate (3×10 mL)
  2. dry with materialThe combined organic phase was dried over magnesium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure
  5. customThe crude residue was purified by medium pressure liquid chromatography

Sources & evidence

ORD record
ord-6257b6a8384e4af4add65e7ab754ab21
Source dataset
uspto-grants-2012_10
Patent number
US08288375B2

Reaction notes

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