Acetic Acid → 3-(1,1-dioxo-4H-1$l^{6},2,4-benzothiadiazin-3-yl)-4-hydroxy-1-isopentyl-1,8-naphthyridin-2-one

HRID 601103ノート

反応式

HRID 601103 の反応式
[CH3:1][CH:2]([CH3:17])[CH2:3][CH2:4][N:5]1[C:10]2[N:11]=[CH:12][CH:13]=[CH:14][C:9]=2[C:8](=[O:15])O[C:6]1=[O:16].[O:18]=[S:19]1(=[O:35])[C:24]2[CH:25]=[CH:26][CH:27]=[CH:28][C:23]=2[NH:22][C:21]([CH2:29]C(OCC)=O)=[N:20]1.[H-].[Na+].C(O)(=O)C>C1COCC1.Cl>[O:35]=[S:19]1(=[O:18])[C:24]2[CH:25]=[CH:26][CH:27]=[CH:28][C:23]=2[NH:22][C:21]([C:29]2[C:6](=[O:16])[N:5]([CH2:4][CH2:3][CH:2]([CH3:1])[CH3:17])[C:10]3[C:9]([C:8]=2[OH:15])=[CH:14][CH:13]=[CH:12][N:11]=3)=[N:20]1

参加物

7

反応物 4

HCID 176Acetic AcidHCID 24758Sodium hydrideHCID 6588352H-1,2,4-Benzothiadiazine-3-acetic acid ethyl ester 1,1-dioxideHCID 102361501-Isopentyl-1H-pyrido[2,3-d][1,3]oxazine-2,4-dione

生成物 1

HCID 1354945853-(1,1-dioxo-4H-1$l^{6},2,4-benzothiadiazin-3-yl)-4-hydroxy-1-isopentyl-1,8-naphthyridin-2-one収率 20%

試薬・触媒・溶媒 2

HCID 313Hydrochloric Acid溶媒HCID 8028Tetrahydrofuran溶媒

反応条件

温度
20 °C

実験手順

To a solution of the product of Example 12A (0.216 g, 0.92 mmol) and the product of Example 1C (0.247 g, 0.922 mmol) in anhydrous THF (7.5 mL) under nitrogen at 20° C. was added sodium hydride (95%, 0.089 g, 3.7 mmol). The reaction was heated at reflux for 3 hours, cooled to 20° C., and added dropwise glacial acetic acid (2.4 mL). The resulting mixture was heated at reflux for 1 hour, cooled to 25° C., and diluted with aqueous hydrochloric acid (0.5 M, 35 mL). The resulting precipitate was collected by filtration, washed with water and dried. The crude product was purified by flash column chromatography on silica gel eluting with hexanes and ethyl acetate (3:1) to give the title compound as a white solid (0.031 g, 20%). MS (ESI−) m/z 411 (M−H)−. The sodium salt of the title compound was prepared according to the procedure of Example 1D. MS (ESI−) m/z 411 (M−H)−. 1H NMR (300 MHz, DMSO-d6) δ 0.95 (s, 3H), 0.98 (s, 3H), 1.47 (m, 2H), 1.64 (m, 1H), 4.30 (t, J=7.72 Hz, 2H), 7.13 (dd, J=7.72, 4.78 Hz, 1H), 7.26 (d, J=8.09 Hz, 1H), 7.30 (d, J=7.72 Hz, 1H), 7.55 (t, J=7.72 Hz, 1H), 7.66 (d, J=8.09 Hz, 1H), 8.37 (dd, J=7.72, 1.84 Hz, 1H), 8.53 (dd, J=4.78, 2.21 Hz, 1H), 15.94 (s, 1H).

後処理

  1. temperatureThe reaction was heated
  2. temperatureat reflux for 3 hours
  3. temperatureThe resulting mixture was heated
  4. temperatureat reflux for 1 hour
  5. temperaturecooled to 25° C.
  6. filtrationThe resulting precipitate was collected by filtration
  7. washwashed with water
  8. customdried
  9. customThe crude product was purified by flash column chromatography on silica gel eluting with hexanes and ethyl acetate (3:1)

出典と根拠

ORDレコード
ord-2051f8941d044664896fc03024bde424
出典データセット
uspto-grants-2011_03
特許番号
US07902203B2

反応ノート

読み込み中…