Sodium Thiosulfate → 3-[(7-Fluoro-5,5-dioxido-3,4-dihydro-2H-1,5-benzoxathiepin-8-yl)oxy]-5-{[(1S)-2-hydroxy-1-methylethyl]oxy}-N-(5-methylpyrazin-2-yl)benzamide

HRID 548770Notes

Reaction equation

HRID 548770 reaction equation
[F:1][C:2]1[C:3]([O:15][C:16]2[CH:17]=[C:18]([CH:29]=[C:30]([O:32][C@@H:33]([CH3:37])[CH2:34][O:35]C)[CH:31]=2)[C:19]([NH:21][C:22]2[CH:27]=[N:26][C:25]([CH3:28])=[CH:24][N:23]=2)=[O:20])=[CH:4][C:5]2[O:11][CH2:10][CH2:9][CH2:8][S:7](=[O:13])(=[O:12])[C:6]=2[CH:14]=1.C[Si](I)(C)C.S([O-])([O-])(=O)=S.[Na+].[Na+]>C(#N)C>[F:1][C:2]1[C:3]([O:15][C:16]2[CH:17]=[C:18]([CH:29]=[C:30]([O:32][C@@H:33]([CH3:37])[CH2:34][OH:35])[CH:31]=2)[C:19]([NH:21][C:22]2[CH:27]=[N:26][C:25]([CH3:28])=[CH:24][N:23]=2)=[O:20])=[CH:4][C:5]2[O:11][CH2:10][CH2:9][CH2:8][S:7](=[O:13])(=[O:12])[C:6]=2[CH:14]=1

Participants

5

Reactant 3

HCID 24477Sodium ThiosulfateHCID 85247Trimethylsilyl iodideHCID 159500413-[(7-Fluoro-5,5-dioxido-3,4-dihydro-2H-1,5-benzoxathiepin-8-yl)oxy]-5-{[(1S)-1-methyl-2-(methyloxy)ethyl]oxy}-N-(5-methylpyrazin-2-yl)benzamide

Product 1

HCID 159501193-[(7-Fluoro-5,5-dioxido-3,4-dihydro-2H-1,5-benzoxathiepin-8-yl)oxy]-5-{[(1S)-2-hydroxy-1-methylethyl]oxy}-N-(5-methylpyrazin-2-yl)benzamideYield 19.3%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A solution of 3-[(7-fluoro-5,5-dioxido-3,4-dihydro-2H-1,5-benzoxathiepin-8-yl)oxy]-5-{[(1S)-1-methyl-2-(methyloxy)ethyl]oxy}-N-(5-methylpyrazin-2-yl)benzamide (100 mg, 0.19 mmol) in acetonitrile (3 mL) was treated with trimethylsilyl iodide (0.138 mL) and stirred at RT under argon for 16 hours. Sodium thiosulphate solution (30 mL) was added and the mixture extracted with ethyl acetate (6×30 mL). The combined organic extracts were dried (MgSO4), filtered and evaporated to give a yellow oil. The oil was chromatographed on alumina, eluting with 0-50% methanol in DCM, to give the desired compound as an orange solid (19 mg). 1H NMR δ (CDCl3): 1.25 (d, 3H), 2.35-2.42 (m, 2H), 2.52 (s, 3H), 3.32-3.41 (m, 2H), 3.46-3.71 (m, 2H), 3.75 (d, 1H), 4.19-4.22 (m, 2H), 4.53-4.57 (m, 1H), 6.78 (d, 1H), 6.80 (t, 1H), 7.18 (s, 1H), 7.35 (s, 1H), 7.80 (d, 1H), 8.18 (s, 1H), 8.37 (s, 1H), 9.50 (s, 1H); m/z 518 (M+H)+, 516 (M−H)−

Workup

  1. extractionthe mixture extracted with ethyl acetate (6×30 mL)
  2. dry with materialThe combined organic extracts were dried (MgSO4)
  3. filtrationfiltered
  4. customevaporated
  5. customto give a yellow oil
  6. customThe oil was chromatographed on alumina
  7. washeluting with 0-50% methanol in DCM

Sources & evidence

ORD record
ord-ca3a119e00af4844a84c488abfeea3ba
Source dataset
uspto-grants-2011_05
Patent number
US07943607B2

Reaction notes

Loading…