Hydrochloric Acid → 6-Fluoro-3-(1-(4-aminobutyl)-4-piperidyl)indole

HRID 478213Notes

Reaction equation

HRID 478213 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][CH2:19][C:20]#[N:21])[CH2:13][CH2:12]3)=[CH:7][NH:8]2)=[CH:4][CH:3]=1.Cl>C(O)C.[Pt]=O>[F:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([CH:11]3[CH2:12][CH2:13][N:14]([CH2:17][CH2:18][CH2:19][CH2:20][NH2:21])[CH2:15][CH2:16]3)=[CH:7][NH:8]2)=[CH:4][CH:3]=1

Participants

5

Reactant 2

HCID 313Hydrochloric AcidHCID 180012406-Fluoro-3-(1-(3-cyanopropyl)-4-piperidyl)indole

Product 1

HCID 180012086-Fluoro-3-(1-(4-aminobutyl)-4-piperidyl)indoleYield 101.5%

Reagents, catalysts & solvents 2

HCID 82844Platinum oxide (PtO)CatalystHCID 702EthanolSolvent

Procedure

To a solution of 6-fluoro-3-(1-(3-cyanopropyl)-4-piperidyl)indole (453 mg, 1.6 mmol) in ethanol (30 mL) was added platinum oxide (110 mg) and a concentrated hydrochloric acid (0.8 mL), and the resulting mixture was stirred under hydrogen atmosphere at room temperature overnight. After filtrating the reaction mixture through Celite, the filtrate was concentrated, and a saturated aqueous sodium hydrogencarbonate was added to pH of 10, and the resulting mixture was extracted with chloroform. After drying over anhydrous sodium sulfate, the chloroform layer was concentrated to afford 6-fluoro-3-(1-(4-aminobutyl)-4-piperidyl)indole (470 mg, yield: 100%) as a pale yellow solid. To a solution of this amine (68 mg, 0.23 mmol) in DMF (0.22 mL) was added lH-pyrazole-1-carboxamidine hydrochloride (35 mg, 0.23 mmol) and diisobutylethylamine (31 mg, 0.23 mmol), and the mixture was stirred at room temperature overnight. After washing with diethyl ether, the reaction mixture was purified by column chromatography on a silica gel (silica gel NH-DM 1020 produced by Fuji Silysia Chemical Ltd., eluent; chloroform:methanol=4:1) to afford a free form (61 mg, yield: 77%) of the title compound as a yellow viscous oil. After adding hydrochloric acid/methanol to a solution of the free form (61 mg) in methanol was concentrated and was then freeze-dried to afford the title compound (53 mg) as a white amorphous solid.

Workup

  1. filtrationAfter filtrating the reaction mixture through Celite
  2. concentrationthe filtrate was concentrated
  3. additiona saturated aqueous sodium hydrogencarbonate was added to pH of 10
  4. extractionthe resulting mixture was extracted with chloroform
  5. dry with materialAfter drying over anhydrous sodium sulfate
  6. concentrationthe chloroform layer was concentrated

Sources & evidence

ORD record
ord-bd4232d0d2604657a297c6aa21758001
Source dataset
uspto-grants-2003_11
Patent number
US06642228B1

Reaction notes

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