Ethanol → HCID 135546394, compound

HRID 1373008Notes

Reaction equation

HRID 1373008 reaction equation
[Na].[N:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]#[N:10])=[CH:4][CH:3]=1.[F:11][C:12]1[CH:13]=[C:14]([CH:17]=[CH:18][CH:19]=1)C=O.Cl.[NH2:21][C:22]([NH2:24])=N.[CH2:25]([OH:27])C>>[NH2:21][C:22]1[NH:24][C:25](=[O:27])[C:8]([C:5]2[CH:6]=[CH:7][N:2]=[CH:3][CH:4]=2)=[C:9]([C:14]2[CH:17]=[CH:18][CH:19]=[C:12]([F:11])[CH:13]=2)[N:10]=1

Participants

6

Reactant 5

HCID 702EthanolHCID 5742Guanidine HydrochlorideHCID 680093-FluorobenzaldehydeHCID 41120852-(Pyridin-4-yl)acetonitrileHCID 5360545Sodium

Product 1

HCID 135546394HCID 135546394, compound

Procedure

Sodium (3.2 g, 139 mmol) was dissolved in ethanol (200 mL), and then 4-pyridylacetonitrile (10.0 g, 64.7 mmol), 3-fluorobenzaldehyde (7.3 mL, 68.8 mmol) and guanidine hydrochloride (7.0 g, 73.3 mmol) were successively added thereto under ice-cooling, followed by heating under reflux for two days. The insoluble matters were filtered off, and the filtrate was concentrated. The residue was subjected to silica gel column chromatography (eluent; dichloromethane, dichloromethane:methanol=20:1, 10:1, 5:1), to give the 5,6-dihydro form of the title compound (13.6 g) as a crude product. To the crude product was added sulfur (26.4 g, 82.3 mmol in terms of sulfur), followed by heating at 185° C. for 2.5 hours. After standing to cool, the reaction mixture was suspended in methanol. The insoluble matters were filtered off and washed with 2N hydrochloric acid. After concentrating methanol from the filtrate, the residue was washed with ethyl acetate twice. The aqueous layer was adjusted to pH 11 with a 5N aqueous sodium hydroxide solution, and washed with ethyl acetate twice. The aqueous layer was neutralized with 2N hydrochloric acid, and the resulting crystals were collected by filtration, and washed with water and ethyl acetate, to give the title compound (6.2 g, 34%) as a colorless solid. In this process, the title compound could also be obtained by isolating (E)-3-(3-fluorophenyl)-2-(4-pyridyl)-2-propenenitrile and then subjecting it to cyclization reaction with guanidine in a manner similar to that described for Referential Example 3.

Workup

  1. temperatureunder ice-cooling
  2. temperatureby heating
  3. temperatureunder reflux for two days
  4. filtrationThe insoluble matters were filtered off
  5. concentrationthe filtrate was concentrated

Sources & evidence

ORD record
ord-4c966840842b4086a641d4ec9fa06263
Source dataset
uspto-grants-2007_01
Patent number
US07160892B2

Reaction notes

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