Pyrazole-1-carboxamidine monohydrochloride → HCID 178479462, compound

HRID 478214Notes

Reaction equation

HRID 478214 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][CH2:20][NH2:21])[CH2:13][CH2:12]3)=[CH:7][NH:8]2)=[CH:4][CH:3]=1.[ClH:22].[N:23]1([C:28](N)=[NH:29])C=CC=N1.C(N(CC(C)C)CC)C(C)C>CN(C=O)C>[ClH:22].[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][NH:21][C:28]([NH2:29])=[NH:23])[CH2:15][CH2:16]3)=[CH:7][NH:8]2)=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 2734672Pyrazole-1-carboxamidine monohydrochlorideHCID 12446309N-Ethyl-2-methyl-N-(2-methylpropyl)propan-1-amineHCID 180012086-Fluoro-3-(1-(4-aminobutyl)-4-piperidyl)indole

Product 1

HCID 178479462HCID 178479462, compoundYield 77%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

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. washAfter washing with diethyl ether
  2. customthe 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)

Sources & evidence

ORD record
ord-4b0ae944e9e8484ca2b7aafd7584d197
Source dataset
uspto-grants-2003_11
Patent number
US06642228B1

Reaction notes

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