Sodium hydride → 3-cyclopentylthio-N-(3,5-dichloropyrid-4-yl)-4-methoxybenzamide

HRID 1489680Notes

Reaction equation

HRID 1489680 reaction equation
[H-].[Na+].[Cl:3][C:4]1[CH:5]=[N:6][CH:7]=[C:8]([Cl:11])[C:9]=1[NH2:10].[CH:12]1([S:17][C:18]2[CH:19]=[C:20]([CH:24]=[CH:25][C:26]=2[O:27][CH3:28])[C:21](Cl)=[O:22])[CH2:16][CH2:15][CH2:14][CH2:13]1.[Cl-].[NH4+]>O1CCCC1>[CH:12]1([S:17][C:18]2[CH:19]=[C:20]([CH:24]=[CH:25][C:26]=2[O:27][CH3:28])[C:21]([NH:10][C:9]2[C:8]([Cl:11])=[CH:7][N:6]=[CH:5][C:4]=2[Cl:3])=[O:22])[CH2:13][CH2:14][CH2:15][CH2:16]1

Participants

6

Reactant 4

HCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 898884-Amino-3,5-dichloropyridineHCID 211879163-Cyclopentylthio-4-methoxybenzoyl chloride

Product 1

HCID 211879333-cyclopentylthio-N-(3,5-dichloropyrid-4-yl)-4-methoxybenzamideYield 18.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent4×

Procedure

A suspension of sodium hydride (60% dispersion in oil; 3.2 g; 80 mmol) in dry tetrahydrofuran (70 mL) under nitrogen at 4° C. is treated with 3,5-dichloro-4-aminopyridine (6.5 g) in dry tetrahydrofuran (80 mL) during 15 minutes and the solution is stirred at room temperature for 1 hour. After cooling to 5° C., it is treated with 3-cyclopentylthio-4-methoxybenzoyl chloride (that is prepared from 9.0 g of 3-cyclopentylthio-4-methoxybenzoic acid as described in Reference Example 47) in dry tetrahydrofuran (80 mL) during 45 minutes, and the temperature is allowed to rise to room temperature. The mixture is treated with a further quantity of tetrahydrofuran (200 mL) and then it is stirred for a further 6 hours. It is then treated with a saturated aqueous solution of ammonium chloride (300 mL), and concentrated in vacuo to low volume. The aqueous residue is extracted with ethyl acetate (2×200 mL). The combined extracts are washed with brine (2×200 mL), dried over magnesium sulfate, and concentrated. The resulting residue is subjected to flash chromatography on silica gel, using a mixture of ethyl acetate and petroleum ether (b.p. 60°-80° C.) (1:1 v/v), to give 3-cyclopentylthio-N-(3,5-dichloropyrid-4-yl)-4-methoxybenzamide (2.5 g), in the form of a colorless solid, m.p. 198° C. [Elemental analysis: C,54.5,H,4.6; N,6.95;S,8.2%; calculated: C,54.4; H,4.6; N,7.05;S,8.1%].

Workup

  1. temperatureAfter cooling to 5° C.
  2. customto rise to room temperature
  3. stirringit is stirred for a further 6 hours
  4. concentrationconcentrated in vacuo to low volume
  5. extractionThe aqueous residue is extracted with ethyl acetate (2×200 mL)
  6. washThe combined extracts are washed with brine (2×200 mL)
  7. dry with materialdried over magnesium sulfate
  8. concentrationconcentrated
  9. additiona mixture of ethyl acetate and petroleum ether (b.p. 60°-80° C.) (1:1 v/v)

Sources & evidence

ORD record
ord-3432a54b620d40b49b52eb29a2d627eb
Source dataset
uspto-grants-1997_10
Patent number
US05679696

Reaction notes

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