Methyl iodide → HCID 136372351, compound

HRID 884237Notes

Reaction equation

HRID 884237 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:36]=[CH:37][C:38]=1[F:39])[CH2:5][N:6]1[C:15](=[O:16])[C:14]([C:17]2[NH:22][C:21]3[CH:23]=[CH:24][C:25]([NH:27][S:28]([CH3:31])(=[O:30])=[O:29])=[CH:26][C:20]=3[S:19](=[O:33])(=[O:32])[N:18]=2)=[C:13]([OH:34])[C@H:12]2[C@@H:7]1[C@H:8]1[CH2:35][C@@H:11]2[CH2:10][CH2:9]1.[C:40](=O)([O-])[O-].[K+].[K+].IC>CN(C)C=O>[F:1][C:2]1[CH:3]=[C:4]([CH:36]=[CH:37][C:38]=1[F:39])[CH2:5][N:6]1[C:15](=[O:16])[C:14]([C:17]2[NH:22][C:21]3[CH:23]=[CH:24][C:25]([N:27]([CH3:40])[S:28]([CH3:31])(=[O:29])=[O:30])=[CH:26][C:20]=3[S:19](=[O:33])(=[O:32])[N:18]=2)=[C:13]([OH:34])[C@H:12]2[C@@H:7]1[C@H:8]1[CH2:35][C@@H:11]2[CH2:10][CH2:9]1

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 11430Potassium CarbonateHCID 135976567HCID 135976567, compound

Product 1

HCID 136372351HCID 136372351, compoundYield 77%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
25 °C

Procedure

N-{3-[(1R,2S,7R,8S)-3-(3,4-Difluoro-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 16, 114 mg, 0.20 mmol) was dissolved in N,N-dimethylformamide (7 mL). Potassium carbonate (55 mg, 0.40 mmol) and iodomethane (0.014 mL, 0.22 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-(3,4-difluoro-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 (94 mg, 0.06 mmol, 77%) as a white powder. 1H NMR (400 MHz, CDCl3) δ: 1.42-1.76 (6H, m), 2.51-2.54 (1H, m), 2.84-2.88 (2H, m), 3.07 (3H, s), 3.38 (3H, s), 3.47-3.49 (1H, m), 5.07-5.10 (2H, m), 6.96-7.16 (3H, m), 7.72-8.01 (3H, m). LC-MS (ESI) calcd for C26H26F2N4O6S2 592.63, found 593.4 [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-2808295bba584108b0d1c265edefe6a8
Source dataset
uspto-grants-2012_08
Patent number
US08236948B2

Reaction notes

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