3-[bis(methylsulfanyl)methylene]-1-isopentyl-2,4(1H,3H)-pyridinedione → 3-(7-amino-1,1-dioxido-4H-1,2,4-benzothiadiazin-3-yl)-4-hydroxy-1-isopentyl-2(1H)-pyridinone

HRID 601421ノート

反応式

HRID 601421 の反応式
CS[C:3](SC)=[C:4]1[C:9](=[O:10])[CH:8]=[CH:7][N:6]([CH2:11][CH2:12][CH:13]([CH3:15])[CH3:14])[C:5]1=[O:16].[NH2:19][C:20]1[CH:25]=[CH:24][C:23]([NH:26]C(=O)OC(C)(C)C)=[CH:22][C:21]=1[S:34]([NH2:37])(=[O:36])=[O:35]>O1CCOCC1>[NH2:26][C:23]1[CH:24]=[CH:25][C:20]2[NH:19][C:3]([C:4]3[C:5](=[O:16])[N:6]([CH2:11][CH2:12][CH:13]([CH3:14])[CH3:15])[CH:7]=[CH:8][C:9]=3[OH:10])=[N:37][S:34](=[O:36])(=[O:35])[C:21]=2[CH:22]=1

参加物

4

反応物 2

HCID 100395903-[bis(methylsulfanyl)methylene]-1-isopentyl-2,4(1H,3H)-pyridinedioneHCID 59805694(4-Amino-3-sulfamoyl-phenyl)-carbamic acid tert-butyl ester

生成物 1

HCID 1363519723-(7-amino-1,1-dioxido-4H-1,2,4-benzothiadiazin-3-yl)-4-hydroxy-1-isopentyl-2(1H)-pyridinone

試薬・触媒・溶媒 1

HCID 312751,4-Dioxane溶媒

反応条件

温度
25 °C

実験手順

The product of Example 457C (2.08 g, 7.29 mmol) was treated with the product of Example 414A (2.00 g, 6.96 mmol) in dioxane (20 mL) at 115° C. for 30 minutes, cooled to 25° C. and concentrated under reduced pressure. A solution of the residue in 4M hydrochloric acid in dioxane (20 mL) was stirred at 25° C. for 18 hours and concentrated under reduced pressure. The residue was triturated with dichloromethane and filtered to give the title compound. The filtrate containing the protected intermediate was concentrated and purified by chromatography on silica gel eluting with 1% methanol in dichloromethane. The protected product was re-subjected to the above deprotection conditions to provide the title compound as its hydrochloride salt (2.02 g, 96%). 1H NMR (300 MHz, DMSO-d6) δ 0.92 (s, 3 H) 0.94 (s, 3 H) 1.58 (m, 3 H) 3.99 (m, 2 H) 6.31 (d, J=7.35 Hz, 1 H) 6.96 (m, 2 H) 7.34 (d, J=8.46 Hz, 1 H) 8.04 (d, J=7.35 Hz, 1 H) 14.04 (s, 1 H) 14.19 (s, 1 H). MS (ESI−) m/z 375 (M−H)−.

後処理

  1. concentrationconcentrated under reduced pressure
  2. concentrationconcentrated under reduced pressure
  3. customThe residue was triturated with dichloromethane
  4. filtrationfiltered

出典と根拠

ORDレコード
ord-da8a6508cbcd4108856087f3625c0017
出典データセット
uspto-grants-2011_03
特許番号
US07902203B2

反応ノート

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