3-Cyclopentyl-3-oxopropanenitrile → HCID 67272039, compound

HRID 1696449Notes

Reaction equation

HRID 1696449 reaction equation
[ClH:1].[CH2:2]([O:4][C:5](=[O:15])[CH2:6][C:7]1[CH:12]=[CH:11][CH:10]=[C:9]([NH:13][NH2:14])[CH:8]=1)[CH3:3].[CH:16]1([C:21](=O)[CH2:22][C:23]#[N:24])[CH2:20][CH2:19][CH2:18][CH2:17]1>Cl>[ClH:1].[CH2:2]([O:4][C:5](=[O:15])[CH2:6][C:7]1[CH:12]=[CH:11][CH:10]=[C:9]([N:13]2[C:23]([NH2:24])=[CH:22][C:21]([CH:16]3[CH2:20][CH2:19][CH2:18][CH2:17]3)=[N:14]2)[CH:8]=1)[CH3:3]

Participants

4

Reactant 2

HCID 135921183-Cyclopentyl-3-oxopropanenitrileHCID 67271852HCID 67271852, compound

Product 1

HCID 67272039HCID 67272039, compoundYield 34%

Reagents, catalysts & solvents 1

HCID 313Hydrochloric AcidSolvent

Procedure

To a mixture of (3-aminophenyl)acetic acid ethyl ester (15 g, 84 mmol) in conc. HCl (20 mL) was added sodium nitrite (6 g, 87 mmol) aqueous solution dropwise under ice-salt bath. The resulting mixture was stirred at 0° C. for 30 min and then added a solution of SnCl2.2H2O (38 g, 168 mmol) in conc. HCl dropwise also at such a rate that the reaction mixture never rose above 5° C. After the addition was completed, the mixture was stirred for another 2 h at room temperature. The precipitate was collected by suction and washed with ethyl ether to afford (3-Hydrazinophenyl)acetic acid ethyl ester hydrochloride (17 g, 88%) as a brown solid. MS (ESI) m/z: 195 (M+H+). A solution of (3-hydrazinophenyl)acetic acid ethyl ester hydrochloride (17 g, 74 mmol) and 3-cyclopentyl-3-oxopropionitrile (12.2 g, 88.8 mol) in alcohol (150 mL) containing conc. HCl (10 mL) was heated to reflux overnight. After removed of the solvent, the precipitate was collected by suction and washed with ethyl ether to afford the crude product, which was purified by column chromatography to afford [3-(5-amino-3-cyclopentylpyrazol-1-yl)phenyl]acetic acid ethyl ester hydrochloride (8.8 g, 34% yield) as a yellow solid. 1H NMR (300 MHz, DMSO-d6): δ 7.40-7.66 (m, 4H), 5.68 (s, 1H), 4.05 (q, J=7.2 Hz, 2H), 3.75 (s, 2H), 3.00-3.08 (m, 1H), 1.98-2.00 (m, 2H), 1.58-1.70 (m, 6H), 1.17 (t, J=7.2 Hz, 3H); MS (ESI) m/z: 314 (M+H+).

Workup

  1. temperaturewas heated
  2. temperatureto reflux overnight
  3. customAfter removed of the solvent
  4. customthe precipitate was collected by suction
  5. washwashed with ethyl ether
  6. customto afford the crude product, which
  7. customwas purified by column chromatography

Sources & evidence

ORD record
ord-80f6cb815db14219b65ba7d5d6b7a38e
Source dataset
uspto-grants-2012_04
Patent number
US08163756B2

Reaction notes

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