Sodium hydride → N-(3,5-dichloropyrid-4-yl)-3-cyclopentyloxy-4-(methylthio)benzamide

HRID 1870345Notes

Reaction equation

HRID 1870345 reaction equation
[NH2:1][C:2]1[C:7]([Cl:8])=[CH:6][N:5]=[CH:4][C:3]=1[Cl:9].[H-].[Na+].[CH:12]1([O:17][C:18]2[CH:19]=[C:20]([CH:24]=[CH:25][C:26]=2[S:27][CH3:28])[C:21](Cl)=[O:22])[CH2:16][CH2:15][CH2:14][CH2:13]1>CN(C)C=O>[Cl:9][C:3]1[CH:4]=[N:5][CH:6]=[C:7]([Cl:8])[C:2]=1[NH:1][C:21](=[O:22])[C:20]1[CH:24]=[CH:25][C:26]([S:27][CH3:28])=[C:18]([O:17][CH:12]2[CH2:13][CH2:14][CH2:15][CH2:16]2)[CH:19]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 898884-Amino-3,5-dichloropyridineHCID 154584173-Cyclopentyloxy-4-(methylthio)benzoyl chloride

Product 1

HCID 15458418N-(3,5-dichloropyrid-4-yl)-3-cyclopentyloxy-4-(methylthio)benzamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

A solution of 4-amino-3,5-dichloropyridine (0.46 g) in dry dimethylformamide (20 mL) is treated with sodium hydride (0.23 g of a 60% dispersion in mineral oil; 2.8 mmol) and the mixture is stirred for 20 minutes. It is then treated with a solution of 3-cyclopentyloxy-4-(methylthio)benzoyl chloride (0.76 g; that is prepared as described in Reference Example 20 in dimethylformamide (10 mL) and stirred at 60° C. for 2 hours. The solution is then concentrated and the resulting residue is partitioned between water (30 mL) and ethyl acetate (50 mL). The aqueous layer is extracted with ethyl acetate (50 mL) and the combined organic layers are dried, concentrated, and subjected to flash chromatography on silica gel, eluting with a mixture of diethyl ether and pentane (1:1 v/v), to give N-(3,5-dichloropyrid-4-yl)-3-cyclopentyloxy-4-(methylthio)benzamide (0.7 g) in the form of a white crystalline solid, m.p. 157-159° C. [NMR (CDCl3):8.57 (s,2H), 7.69 (bs,1H), 7.47 (dd,1H,J=8 Hz,J=2 Hz), 7.43 (d,1H,J=2 Hz), 7.17 (d,1H,J=8 Hz), 4.95 (m,1H), 2.46 (s,3H), 1.98-1.6(m,8H): Elemental analysis: C,54.0; H,4.5; N,7.0; Cl,17.8%; calculated: C,54.4; H,4.6; N,7.05; Cl,17.85%].

Workup

  1. customthat is prepared
  2. stirringstirred at 60° C. for 2 hours
  3. concentrationThe solution is then concentrated
  4. customthe resulting residue is partitioned between water (30 mL) and ethyl acetate (50 mL)
  5. extractionThe aqueous layer is extracted with ethyl acetate (50 mL)
  6. customthe combined organic layers are dried
  7. concentrationconcentrated
  8. washeluting with a mixture of diethyl ether and pentane (1:1 v/v)

Sources & evidence

ORD record
ord-7afa13ee8d35437aa2256412f43fc559
Source dataset
uspto-grants-2000_08
Patent number
US06096768

Reaction notes

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