Water → HCID 57731941、化合物

HRID 1808163

反応式

HRID 1808163 の反応式
[F:1][C:2]1[CH:7]=[C:6]([C:8]([NH:10][CH2:11][C:12]([O:15][C:16]2[CH:21]=[CH:20][C:19]([F:22])=[CH:18][CH:17]=2)([CH3:14])[CH3:13])=[O:9])[CH:5]=[CH:4][C:3]=1[S:23](Cl)(=[O:25])=[O:24].[S:27]1[C:31]([NH2:32])=[N:30][CH:29]=[N:28]1.[OH-].[Na+].O1CCOCC1.O>>[F:1][C:2]1[CH:7]=[C:6]([CH:5]=[CH:4][C:3]=1[S:23]([NH:32][C:31]1[S:27][N:28]=[CH:29][N:30]=1)(=[O:25])=[O:24])[C:8]([NH:10][CH2:11][C:12]([O:15][C:16]1[CH:21]=[CH:20][C:19]([F:22])=[CH:18][CH:17]=1)([CH3:14])[CH3:13])=[O:9]

参加物

6

反応物 5

HCID 962WaterHCID 14798Sodium HydroxideHCID 312751,4-DioxaneHCID 2902745-Amino-1,2,4-thiadiazoleHCID 577319902-Fluoro-4-({[2-(4-fluorophenoxy)-2-methylpropyl]amino}carbonyl)benzenesulfonyl chloride

生成物 1

HCID 57731941HCID 57731941、化合物収率 17.1%

実験手順

2-Fluoro-4-({[2-(4-fluorophenoxy)-2-methylpropyl]amino}carbonyl)benzenesulfonyl chloride (Preparation 95, 242 mg, 0.599 mmol) was added portion-wise to a solution of 1,2,4-thiadiazol-5-amine (182 mg, 1.80 mmol) and sodium hydroxide (71.9 mg, 1.80 mmol) in 1,4-dioxane (1.9 mL, 24 mmol) and water (0.37 mL, 21 mmol). After stirring 30 min at ambient temperature, the reaction was quenched with 2 N HCl. The mixture was partitioned with methylene chloride. The aqueous layer was washed with methylene chloride, and the combined organic layers were dried over sodium sulfate, filtered and concentrated onto Celite. The residue was purified via automated flash chromatography (12 g SiO2, chloroform to 20% MeOH in chloroform). The product containing fractions were concentrated in vacuo, and the residue was dissolved in 1 mL of DMSO, filtered, and purified via reverse-phase HPLC (Prep: Phenomenex 250×30.0 mm 15 micron C18 column. 40 mL/min. Gradient 15% B to 100% B over 25 min. Solvent A: 7800 water/200 acetonitrile/8 TFA. Solvent B: 7200 acetonitrile/800 water/8 TFA). The product containing fractions were lyophilized to afford the product as a white powder (48 mg, 16%).

後処理

  1. customthe reaction was quenched with 2 N HCl
  2. customThe mixture was partitioned with methylene chloride
  3. washThe aqueous layer was washed with methylene chloride
  4. dry with materialthe combined organic layers were dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated onto Celite
  7. customThe residue was purified
  8. additionThe product containing fractions
  9. concentrationwere concentrated in vacuo
  10. dissolutionthe residue was dissolved in 1 mL of DMSO
  11. filtrationfiltered
  12. custompurified via reverse-phase HPLC (Prep: Phenomenex 250×30.0 mm 15 micron C18 column. 40 mL/min. Gradient 15% B to 100% B over 25 min. Solvent A: 7800 water/200 acetonitrile/8 TFA. Solvent B: 7200 acetonitrile/800 water/8 TFA)
  13. additionThe product containing fractions

出典と根拠

ORDレコード
ord-6b268d057bab4b94bddac03654c1a18d
出典データセット
uspto-grants-2013_01
特許番号
US08357711B2

関連ノート

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