Maleic Acid → HCID 178505429, compound

HRID 1449980Notes

Reaction equation

HRID 1449980 reaction equation
Cl.[F:2][C:3]1[CH:11]=[C:10]2[C:6]([C:7]([CH:12]3[CH2:17][CH2:16][N:15]([CH2:18][CH2:19][N:20]4[C:24](=O)[C:23]5=[CH:26][CH:27]=[CH:28][CH:29]=[C:22]5[C:21]4=O)[CH2:14][CH2:13]3)=[N:8][NH:9]2)=[CH:5][CH:4]=1.[H-].[Al+3].[Li+].[H-].[H-].[H-].[C:37]([OH:44])(=[O:43])/[CH:38]=[CH:39]\[C:40]([OH:42])=[O:41]>C1COCC1.CO>[C:37]([OH:44])(=[O:43])/[CH:38]=[CH:39]\[C:40]([OH:42])=[O:41].[C:37]([OH:44])(=[O:43])/[CH:38]=[CH:39]\[C:40]([OH:42])=[O:41].[F:2][C:3]1[CH:11]=[C:10]2[C:6]([C:7]([CH:12]3[CH2:17][CH2:16][N:15]([CH2:18][CH2:19][N:20]4[CH2:24][C:23]5[C:22](=[CH:29][CH:28]=[CH:27][CH:26]=5)[CH2:21]4)[CH2:14][CH2:13]3)=[N:8][NH:9]2)=[CH:5][CH:4]=1

Participants

6

Reactant 3

HCID 444266Maleic AcidHCID 21226445Aluminium lithium hydrideHCID 178479599HCID 178479599, compound

Product 1

HCID 178505429HCID 178505429, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of N-[2-[4-(6-fluoro-1H-indazol-3-yl)-1-piperidinyl]ethyl]phthalimide hydrochloride (Example 183) (3.1 g, 7.91 mmol) in THF (100 ml) was added lithium aluminum hydride (16.6 ml of a 1.0M solution in THF, 16.6 mmol) at room temperature, under nitrogen. The reaction mixture was warmed to reflux for 6.5 hours and cooled to room temperature. The reaction was quenched with water (1.5 ml, dropwise) and the precipitated salts were removed via filtration. The solids were washed with DCM and the combined filtrates concentrated to give 2.5 g of the crude product as a solid. The dimaleate salt was prepared in methanol using 3.5 g (>4.0 e.q.) of maleic acid. The light green precipitate was collected via filtration and washed with methanol. Recrystallization from methanol gave 2.1 g of the desired product as an off-white solid, m.p. 196°-199° C. ANALYSIS: Calculated for C22H25FN4.2C4H4O4 : 60.40%C 5.58%H 9.39%N Found: 60.33%C 5.42%H 9.42%N

Workup

  1. temperatureThe reaction mixture was warmed
  2. temperatureto reflux for 6.5 hours
  3. customThe reaction was quenched with water (1.5 ml
  4. customdropwise) and the precipitated salts were removed via filtration
  5. washThe solids were washed with DCM
  6. concentrationthe combined filtrates concentrated
  7. customto give 2.5 g of the crude product as a solid
  8. filtrationThe light green precipitate was collected via filtration
  9. washwashed with methanol
  10. customRecrystallization from methanol

Sources & evidence

ORD record
ord-84d9f466920245f69ff2a8abf622af36
Source dataset
uspto-grants-1997_02
Patent number
US05599821

Reaction notes

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