Tetrahydrofuran → N-(7-(5-fluoro-2-methylphenyl)-5-(methylsulfonyl)-2,6-naphthyridin-3-yl)cyclopropanecarboxamide

HRID 468873ノート

反応式

HRID 468873 の反応式
Cl[C:2]1[N:11]=[C:10]([C:12]2[CH:17]=[C:16]([F:18])[CH:15]=[CH:14][C:13]=2[CH3:19])[CH:9]=[C:8]2[C:3]=1[CH:4]=[C:5]([NH:20][C:21]([CH:23]1[CH2:25][CH2:24]1)=[O:22])[N:6]=[CH:7]2.[CH3:26]SC.[Na].O1CCCC1.O[O:36][S:37]([O-:39])=O.[K+]>ClCCl.CO>[F:18][C:16]1[CH:15]=[CH:14][C:13]([CH3:19])=[C:12]([C:10]2[CH:9]=[C:8]3[C:3]([CH:4]=[C:5]([NH:20][C:21]([CH:23]4[CH2:25][CH2:24]4)=[O:22])[N:6]=[CH:7]3)=[C:2]([S:37]([CH3:26])(=[O:39])=[O:36])[N:11]=2)[CH:17]=1

参加物

7

反応物 4

HCID 8028TetrahydrofuranHCID 23707502Potassium hydroxy sulfiteHCID 57410130HCID 57410130、化合物HCID 86593196Sodium methylsulfide

生成物 1

HCID 67976360N-(7-(5-fluoro-2-methylphenyl)-5-(methylsulfonyl)-2,6-naphthyridin-3-yl)cyclopropanecarboxamide収率 50%

試薬・触媒・溶媒 2

HCID 887Methanol溶媒HCID 6344Dichloromethane溶媒2 回

反応条件

温度
75 °C

実験手順

A mixture of N-(5-chloro-7-(5-fluoro-2-methylphenyl)-2,6-naphthyridin-3-yl)cyclopropanecarboxamide (40 mg, 0.1 mmol), sodium methyl sulfide (12 mg, 0.17 mmol) and tetrahydrofuran (1 mL) was heated at 75° C. for 30 minutes. The mixture was diluted with dichloromethane (50 mL) and washed with water (20 mL). The organic layer was separated, dried over sodium sulfate, filtered, and evaporated in vacuo to afford a residue that was redissolved in methanol (1 mL) and treated with Oxone® (270 mg, 0.45 mmol). The reaction was mixed at room temperature for 2 hours and then diluted with dichloromethane (50 mL) and washed with water (20 mL). The organic layer was separated, dried over sodium sulfate, filtered, and evaporated in vacuo to afford a residue that was purified by reverse phase HPLC (5-85% acetonitrile in water with 0.1% formic acid over 14 min) to afford the title compound as an off-white solid (10 mg, 50%). 1H NMR (400 MHz, DMSO) δ 11.30 (s, 1H), 9.50 (s, 1H), 9.36 (s, 1H), 8.52 (s, 1H), 7.54-7.37 (m, 2H), 7.26 (m, 1H), 3.55 (s, 3H), 2.43 (s, 3H), 2.11 (m, 1H), 0.97-0.79 (m, 4H). LCMS (Method E): RT=4.997 min, M+H+=400.1.

後処理

  1. washwashed with water (20 mL)
  2. customThe organic layer was separated
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. customevaporated in vacuo
  6. customto afford a residue that
  7. additionThe reaction was mixed at room temperature for 2 hours
  8. washwashed with water (20 mL)
  9. customThe organic layer was separated
  10. dry with materialdried over sodium sulfate
  11. filtrationfiltered
  12. customevaporated in vacuo
  13. customto afford a residue that
  14. customwas purified by reverse phase HPLC (5-85% acetonitrile in water with 0.1% formic acid over 14 min)

出典と根拠

ORDレコード
ord-b1083032d2dc47889e38560060036156
出典データセット
uspto-grants-2014_01
特許番号
US08623889B2

反応ノート

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