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

HRID 1502390노트

반응식

HRID 1502390 반응식
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

참가 물질

7

반응물 4

HCID 8028TetrahydrofuranHCID 23707502Potassium hydroxy sulfiteHCID 57410130HCID 57410130, 화합물HCID 86593196Sodium methylsulfide

생성물 1

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

시약·촉매·용매 2

HCID 887Methanol용매HCID 6344Dichloromethane용매2회

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온도
75 °C

실험 절차

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.

후처리

  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)

출처 및 근거

ORD 기록
ord-3c92331d1a6f4efeae257a44af35ed0b
출처 데이터셋
uspto-grants-2015_12
특허 번호
US09206175B2

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