1,3-Isobenzofurandione, 5-fluoro- → HCID 178515089, compound

HRID 55695

Reaction equation

HRID 55695 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)[O:27][C:25](=[O:26])[C:24]2=[CH:30][CH:31]=1.C(Cl)Cl.CO>CN(C=O)C>[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 178515089HCID 178515089, compoundYield 37.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution consisting of 2-[4-(6-fluoro-1H-indazol-3-yl)-1-piperidinyl]ethylamine (6.1 g, 23.2 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 (<0.5 mmHg, 55 C.) 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 4-fluoro-N-[2-[4-(6-fluoro-1H-indazol-3-yl)-1-piperidinyl]ethyl]phthalimide. To a solution of the latter compound (3.6 g 8.8 mmol) in anhydrous THF (100 ml) was added LAH (18.4 ml of a 1.0M solution in THF, 18.4 mmol) at room temperature, under nitrogen. The reaction mixture was warmed to reflux for 4 hours. Upon cooling to room temperature, the reaction was quenched with water (1.5 ml, dropwise). The precipitated salts were removed via filtration and washed with DCM. The combined filtrates were concentrated to give a solid which was purified via flash column chromatography (silica gel, 0-8% MeOH/DCM). The product containing fractions were concentrated to give 2.4 g product as an off-white solid. The dimaleate salt was prepared in methanol using 2.4 eq. of maleic acid. The white precipitate was collected via filtration and washed with methanol, m.p. 186°-188° C.

Workup

  1. temperatureThe reaction mixture was warmed to 80 C
  2. customThe DMF was removed under reduced pressure (<0.5 mmHg, 55 C.)
  3. customto give a brown oil which
  4. customPurification via flash column chromatography (silica gel, 2% MeOH/DCM)

Sources & evidence

ORD record
ord-df9ea26c86ec42ee8ea5014d1e86fb3c
Source dataset
uspto-grants-1997_04
Patent number
US05624927

Linked notes

Loading…