1,3-Isobenzofurandione, 5-fluoro- → 4-Fluoro-N-[2-[4-(6-fluoro-1H-indazol-3-yl)1-piperidinyl]ethyl]phthalimide maleate

HRID 265562Notes

Reaction equation

HRID 265562 reaction equation
[F:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([CH:11]3[CH2:16][CH2:15][N:14]([CH2:17][CH2:18][NH2:19])[CH2:13][CH2:12]3)=[N:7][NH:8]2)=[CH:4][CH:3]=1.[F:20][C:21]1[CH:22]=[C:23]2[C:28](=[O:29])[O:27][C:25](=[O:26])[C:24]2=[CH:30][CH:31]=1.C(Cl)Cl.C[OH:36]>CN(C=O)C>[C:28]([OH:27])(=[O:29])/[CH:23]=[CH:24]\[C:25]([OH:26])=[O:36].[F:20][C:21]1[CH:22]=[C:23]2[C:28](=[O:27])[N:19]([CH2:18][CH2:17][N:14]3[CH2:13][CH2:12][CH:11]([C:6]4[C:5]5[C:9](=[CH:10][C:2]([F:1])=[CH:3][CH:4]=5)[NH:8][N:7]=4)[CH2:16][CH2:15]3)[C:25](=[O:26])[C:24]2=[CH:30][CH:31]=1

Participants

5

Reactant 3

HCID 675721,3-Isobenzofurandione, 5-fluoro-HCID 21226129Dichloromethane methanolHCID 178511315HCID 178511315, compound

Product 1

HCID 1785255264-Fluoro-N-[2-[4-(6-fluoro-1H-indazol-3-yl)1-piperidinyl]ethyl]phthalimide maleate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 2-[4-(6-fluoro-1H-3-indazolyl)-1-piperidinyl]ethylamine (6.1 g, 23.3 mmol) in DMF (230 ml) was added 4-fluorophthalic anhydride (4.2 g, 25.5 mmol) at room temperature under nitrogen. The reaction mixture was warmed to 80 C. for 2.5 hours at which time it was allowed to cool to room temperature. The DMF was removed under reduced pressure to give a brown oil which was dissolved into DCM/MeOH. Purification via flash column chromatography (silica gel, 2% MeOH/DCM) afforded 3.6 g of the desired product as a white solid. The maleate salt was prepared in methanol (75 ml) using maleic acid (2.1 eq.). The precipitated salt was collected via filtration and recrystallized from acetonitrile to give a white solid, m.p. 193°-195° C.

Workup

  1. temperatureThe reaction mixture was warmed to 80 C
  2. customThe DMF was removed under reduced pressure
  3. customto give a brown oil which
  4. customPurification via flash column chromatography (silica gel, 2% MeOH/DCM)

Sources & evidence

ORD record
ord-3240278a31d74439b3fc70c32b16218d
Source dataset
uspto-grants-1997_07
Patent number
US05648363

Reaction notes

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