Sodium hydride → 1-[3-(Dimethylamino)propyl]-3-(1-methyl-4-piperidinyl)-1H-indazole difumarate

HRID 986112Notes

Reaction equation

HRID 986112 reaction equation
[H-].[Na+].[CH3:3][N:4]1[CH2:9][CH2:8][CH:7]([C:10]2[C:18]3[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=3)[NH:12][N:11]=2)[CH2:6][CH2:5]1.[CH3:19][N:20]([CH2:22][CH2:23][CH2:24]Cl)[CH3:21].[C:26]([OH:33])(=[O:32])/[CH:27]=[CH:28]/[C:29]([OH:31])=[O:30]>CN(C)C=O.C1(C)C=CC=CC=1.C(#N)C.O>[C:26]([OH:33])(=[O:32])/[CH:27]=[CH:28]/[C:29]([OH:31])=[O:30].[C:26]([OH:33])(=[O:32])/[CH:27]=[CH:28]/[C:29]([OH:31])=[O:30].[CH3:19][N:20]([CH3:21])[CH2:22][CH2:23][CH2:24][N:12]1[C:13]2[C:18](=[CH:17][CH:16]=[CH:15][CH:14]=2)[C:10]([CH:7]2[CH2:6][CH2:5][N:4]([CH3:3])[CH2:9][CH2:8]2)=[N:11]1

Participants

9

Reactant 4

HCID 24758Sodium hydrideHCID 669603-Chloro-N,N-dimethyl-1-propanamineHCID 444972Fumaric AcidHCID 178480237HCID 178480237, compound

Product 1

HCID 140325031-[3-(Dimethylamino)propyl]-3-(1-methyl-4-piperidinyl)-1H-indazole difumarateYield 18.7%

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 1140TolueneSolventHCID 6228DimethylformamideSolvent2×HCID 6342AcetonitrileSolvent

Procedure

To a stirred suspension of 1.15 g of sodium hydride (50% oil dispersion) in 30 ml of dimethylformamide, under nitrogen, was added dropwise 4.3 g of 3-(1-methyl-4-piperidinyl)-1H-indazole dissolved in 30 ml of hot dimethylformamide. After stirring at ambient temperature for 1 hr, a solution of 3.3 g of dimethylaminopropylchloride in 30 ml of toluene was added dropwise. The reaction was then heated at 60° for 1 hr and then stirred at ambient temperature for 16 hrs. The reaction mixture was poured into water and the aqueous suspension was extracted with ethyl acetate (3×150 ml). The organic extracts were combined, washed with water, brine, dried over anhydrous magnesium sulfate, and the solvent evaporated in vacuo to yield an oil. The oil was dissolved in 25 ml of acetonitrile and 4.6 g of fumaric acid was added. The mixture was warmed on the steam bath (ca. 15 min), and then left at ambient temperature for 15 hrs. The resultant solid was filtered and recrystallized from dimethylformaide (thrice) with cooling (ca. 5°) to yield 1.4 g (18.7%) of product, mp 161°-163° C.

Workup

  1. temperatureThe reaction was then heated at 60° for 1 hr
  2. stirringstirred at ambient temperature for 16 hrs
  3. extractionthe aqueous suspension was extracted with ethyl acetate (3×150 ml)
  4. washwashed with water, brine
  5. dry with materialdried over anhydrous magnesium sulfate
  6. customthe solvent evaporated in vacuo
  7. customto yield an oil
  8. temperatureThe mixture was warmed on the steam bath (ca. 15 min)
  9. waitleft at ambient temperature for 15 hrs
  10. filtrationThe resultant solid was filtered
  11. customrecrystallized from dimethylformaide (thrice)
  12. temperaturewith cooling (ca. 5°)

Sources & evidence

ORD record
ord-baeea974193d4d8bb50183923ea973cf
Source dataset
uspto-grants-1987_12
Patent number
US04710573

Reaction notes

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