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

HRID 1383480ノート

反応式

HRID 1383480 の反応式
[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

参加物

6

反応物 4

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

生成物 1

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

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒4 回

実験手順

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%].

後処理

  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)

出典と根拠

ORDレコード
ord-6c5f29eeb4b04e02a67b8d4d1f12710a
出典データセット
uspto-grants-2001_07
特許番号
US06255326B1

反応ノート

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