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

HRID 1502390Notes

Reaction equation

HRID 1502390 reaction equation
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

Participants

7

Reactant 4

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

Product 1

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

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
75 °C

Procedure

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.

Workup

  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)

Sources & evidence

ORD record
ord-3c92331d1a6f4efeae257a44af35ed0b
Source dataset
uspto-grants-2015_12
Patent number
US09206175B2

Reaction notes

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