Diisopropylethylamine → 1-[3-(3-Fluoro-phenylamino)-6,7-dimethoxy-4H-indeno[1,2-c]pyrazol-1-yl]-2-hydroxy-ethanone

HRID 1714445

Reaction equation

HRID 1714445 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:20](=[CH:21][C:22]=1[O:23][CH3:24])[C:8]1[NH:9][N:10]=[C:11]([NH:12][C:13]3[CH:18]=[CH:17][CH:16]=[C:15]([F:19])[CH:14]=3)[C:7]=1[CH2:6]2.C([O:32][CH2:33][C:34](Cl)=[O:35])C1C=CC=CC=1.C(N(C(C)C)CC)(C)C>CN(C=O)C>[F:19][C:15]1[CH:14]=[C:13]([NH:12][C:11]2[C:7]3[CH2:6][C:5]4[C:20](=[CH:21][C:22]([O:23][CH3:24])=[C:3]([O:2][CH3:1])[CH:4]=4)[C:8]=3[N:9]([C:33](=[O:32])[CH2:34][OH:35])[N:10]=2)[CH:18]=[CH:17][CH:16]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 177085Benzyloxyacetyl chloride2×HCID 9797370Jnj-101984092×

Product 1

HCID 184454401-[3-(3-Fluoro-phenylamino)-6,7-dimethoxy-4H-indeno[1,2-c]pyrazol-1-yl]-2-hydroxy-ethanoneYield 90%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a mixture of (6,7-Dimethoxy-1,4-dihydro-indeno[1,2-c]pyrazol-3-yl)-(3-fluoro-phenyl)-amine (Compound 14) (3.6 g, 10.0 mmol), Benzyloxy-acetyl chloride (Compound 27a) (2.2 g, 12.0 mmole) and DMF (50 mL) was added Diisopropylethylamine (5.2 mL, 30 mmole) at room temperature with stirring. The reaction was stirred at room temperature over night. The reaction was quenched with water and extracted with EtOAc. Dried over sodium sulfate and removed solvent in vacuo. The crude material was then taken up into ethanol and 0.5 g of Pd/C was added. The reaction was shaken on the hydrogenator over night. The reaction was filtered through Celite and removed solvent in vacuo. Triturated in a small amount of EtOAc. 3.2 g of ˜90% pure material was produced. 300 mg of the crude material was prepped on the Gilson and lyophilization gave Compound 432 as a white powder. MS m/z 384 (M+H)+;

Workup

  1. stirringThe reaction was stirred at room temperature over night
  2. customThe reaction was quenched with water
  3. extractionextracted with EtOAc
  4. dry with materialDried over sodium sulfate
  5. customremoved solvent in vacuo
  6. additionwas added
  7. stirringThe reaction was shaken on the hydrogenator over night
  8. filtrationThe reaction was filtered through Celite
  9. customremoved solvent in vacuo
  10. customTriturated in a small amount of EtOAc

Sources & evidence

ORD record
ord-41a048ca666d4737ab84fdaaccf78c5f
Source dataset
uspto-grants-2010_09
Patent number
US07795440B2

Linked notes

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