Sodium hydride → 2-({4-[(4-Acetylpiperazin-1-yl)methyl]-6-methoxypyridin-2-yl}amino)-1,3-thiazole-5-carbonitrile

HRID 1355474ノート

反応式

HRID 1355474 の反応式
[C:1]([N:4]1[CH2:9][CH2:8][N:7]([CH2:10][C:11]2[CH:16]=[C:15]([O:17][CH3:18])[N:14]=[C:13]([NH:19][C:20](=O)OC(C)(C)C)[CH:12]=2)[CH2:6][CH2:5]1)(=[O:3])[CH3:2].[H-].[Na+].ClC1[S:31][C:32]([C:35]#[N:36])=[CH:33][N:34]=1>Cl.O1CCOCC1.O.C([O-])(O)=O.[Na+]>[C:1]([N:4]1[CH2:5][CH2:6][N:7]([CH2:10][C:11]2[CH:16]=[C:15]([O:17][CH3:18])[N:14]=[C:13]([NH:19][C:20]3[S:31][C:32]([C:35]#[N:36])=[CH:33][N:34]=3)[CH:12]=2)[CH2:8][CH2:9]1)(=[O:3])[CH3:2]

参加物

8

反応物 3

HCID 24758Sodium hydrideHCID 14852222-Chlorothiazole-5-carbonitrileHCID 18506936tert-Butyl 4-[(4-acetylpiperazin-1-yl)methyl]-6-methoxypyridin-2-ylcarbamate

生成物 1

HCID 185068202-({4-[(4-Acetylpiperazin-1-yl)methyl]-6-methoxypyridin-2-yl}amino)-1,3-thiazole-5-carbonitrile

試薬・触媒・溶媒 4

HCID 313Hydrochloric Acid溶媒HCID 962Water溶媒HCID 312751,4-Dioxane溶媒HCID 516892Sodium Bicarbonate溶媒

実験手順

tert-Butyl 4-[(4-acetylpiperazin-1-yl)methyl]-6-methoxypyridin-2-ylcarbamate (15-4, 310 mg, 0.85 mmole) was taken up in 4 M HCl in dioxane (15 mL) at RT. After 4 hr the mixture was diluted with H2O and neutralized with solid NaHCO3. The resulting mixture was extracted with CH2Cl2 (3×). The combined organic layers were dried (MgSO4), filtered, and concentrated. The residue was taken up in dry THF (5 mL). To this was added NaH (90 mg, 60% dispersion in mineral oil, 2.13 mmole). After gas evolution had ceased 2-chloro-5-cyano-1,3-thiazole (185 mg, 1.28 mmole) was added and the mixture heated to reflux. After 2.5 hr the mixture was cooled to RT and quenched with saturated NH4Cl. The layers were separated and the aqueous layer extracted with CH2Cl2 (4×). The combined organic layers were dried (MgSO4), filtered, and concentrated. Flash column chromatography (gradient, 0-15% EtOH/EtOAc) gave the titled compound as a tan solid. 1H-NMR (500 MHz, d6-DMSO) δ8.26 (s, 1H), 6.70 (s, 1H), 6.43 (s, 1H), 4.04 (s, 3H), 3.47 (s, 2H), 3.43 (m, 4H), 2.38 (m, 2H), 2.31 (m, 2H), 1.98 (s, 3H); MS (ES) (M+H)+373.

後処理

  1. extractionThe resulting mixture was extracted with CH2Cl2 (3×)
  2. dry with materialThe combined organic layers were dried (MgSO4)
  3. filtrationfiltered
  4. concentrationconcentrated
  5. additionwas added
  6. temperaturethe mixture heated to reflux
  7. customquenched with saturated NH4Cl
  8. customThe layers were separated
  9. extractionthe aqueous layer extracted with CH2Cl2 (4×)
  10. dry with materialThe combined organic layers were dried (MgSO4)
  11. filtrationfiltered
  12. concentrationconcentrated

出典と根拠

ORDレコード
ord-f5221b39af8d489781f92ae426f3acff
出典データセット
uspto-grants-2003_07
特許番号
US06586423B2

反応ノート

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