Methyl iodide → N-{3-[(1R,2S,7R,8S)-3-(4-fluoro-3-methyl-benzyl)-6-hydroxy-4-oxo-3-aza-tricyclo[6.2.1.02,7]undec-5-en-5-yl]-1,1-dioxo-1,4-dihydro-1lambda6-benzo[1,2,4]thiadiazin-7-yl}-N-methyl-methanesulfonamide

HRID 548320Notes

Reaction equation

HRID 548320 reaction equation
[F:1][C:2]1[CH:38]=[CH:37][C:5]([CH2:6][N:7]2[C:16](=[O:17])[C:15]([C:18]3[NH:23][C:22]4[CH:24]=[CH:25][C:26]([NH:28][S:29]([CH3:32])(=[O:31])=[O:30])=[CH:27][C:21]=4[S:20](=[O:34])(=[O:33])[N:19]=3)=[C:14]([OH:35])[C@H:13]3[C@@H:8]2[C@H:9]2[CH2:36][C@@H:12]3[CH2:11][CH2:10]2)=[CH:4][C:3]=1[CH3:39].[C:40](=O)([O-])[O-].[K+].[K+].IC>CN(C)C=O>[F:1][C:2]1[CH:38]=[CH:37][C:5]([CH2:6][N:7]2[C:16](=[O:17])[C:15]([C:18]3[NH:23][C:22]4[CH:24]=[CH:25][C:26]([N:28]([CH3:40])[S:29]([CH3:32])(=[O:31])=[O:30])=[CH:27][C:21]=4[S:20](=[O:33])(=[O:34])[N:19]=3)=[C:14]([OH:35])[C@H:13]3[C@@H:8]2[C@H:9]2[CH2:36][C@@H:12]3[CH2:11][CH2:10]2)=[CH:4][C:3]=1[CH3:39]

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 11430Potassium CarbonateHCID 135976571N-{3-[(1R,2S,7R,8S)-3-(4-fluoro-3-methyl-benzyl)-6-hydroxy-4-oxo-3-aza-tricyclo[6.2.1.02,7]undec-5-en-5-yl]-1,1-dioxo-1,4-dihydro-1lambda6-benzo[1,2,4]thiadiazin-7-yl}-methanesulfonamide

Product 1

HCID 136402496N-{3-[(1R,2S,7R,8S)-3-(4-fluoro-3-methyl-benzyl)-6-hydroxy-4-oxo-3-aza-tricyclo[6.2.1.02,7]undec-5-en-5-yl]-1,1-dioxo-1,4-dihydro-1lambda6-benzo[1,2,4]thiadiazin-7-yl}-N-methyl-methanesulfonamideYield 96%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
25 °C

Procedure

N-{3-[(1R,2S,7R,8S)-3-(4-Fluoro-3-methyl-benzyl)-6-hydroxy-4-oxo-3-aza-tricyclo[6.2.1.02,7]undec-5-en-5-yl]-1,1-dioxo-1,4-dihydro-1λ6-benzo[1,2,4]thiadiazin-7-yl}-methanesulfonamide (prepared as described in Example 15, 92 mg, 0.16 mmol) was dissolved in N,N-dimethylformamide (6 mL). Potassium carbonate (44 mg, 0.32 mmol) and iodomethane (0.011 mL, 0.18 mmol) were added sequentially. The reaction was stirred at 25° C. for 18 h. The reaction was quenched via the addition of 1.0 M aqueous hydrochloric acid solution (20 mL). The mixture was extracted with ethyl acetate (3×30 mL). The combined organic layers were washed with saturated aqueous brine solution (20 mL), dried over magnesium sulfate, filtered, and concentrated in vacuo to afford a golden oil. Purification by flash column chromatography (Teledyne Isco RediSep column; 0 to 20% ethyl acetate in dichloromethane) afforded the desired product, N-{3-[(1R,2S,7R,8S)-3-(4-fluoro-3-methyl-benzyl)-6-hydroxy-4-oxo-3-aza-tricyclo[6.2.1.02,7]undec-5-en-5-yl]-1,1-dioxo-1,4-dihydro-1λ6-benzo[1,2,4]thiadiazin-7-yl}-N-methyl-methanesulfonamide (91 mg, 0.15 mmol, 96%), as a white powder. 1H NMR (400 MHz, CDCl3) δ: 1.18-2.85 (9H, m), 2.90 (3H, s), 2.97 (3H, s), 3.38 (3H, s), 3.45-3.47 (1H, m), 5.17-5.21 (2H, m), 6.96-7.08 (3H, m), 7.72-8.02 (3H, m). LC-MS (ESI) calcd for C27H29FN4O6S2 588.67, found 589.2 [M+H+].

Workup

  1. customThe reaction was quenched via the addition of 1.0 M aqueous hydrochloric acid solution (20 mL)
  2. extractionThe mixture was extracted with ethyl acetate (3×30 mL)
  3. washThe combined organic layers were washed with saturated aqueous brine solution (20 mL)
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customto afford a golden oil
  8. customPurification by flash column chromatography (Teledyne Isco RediSep column; 0 to 20% ethyl acetate in dichloromethane)

Sources & evidence

ORD record
ord-60542a20ef4645409b0b3750a8a49530
Source dataset
uspto-grants-2011_05
Patent number
US07939524B2

Reaction notes

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