benzyl (N-{3-[(1R,2S,7R,8S)-3-(4-fluoro-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-thieno[2,3-e][1,2,4]thiadiazin-7-ylmethyl}amino)sulfonylcarbamate → N-{3-[(1R,2S,7R,8S)-3-(4-fluoro-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-thieno[2,3-e][1,2,4]thiadiazin-7-ylmethyl}-sulfamide

HRID 1516031Notes

Reaction equation

HRID 1516031 reaction equation
[F:1][C:2]1[CH:48]=[CH:47][C:5]([CH2:6][N:7]2[C:16](=[O:17])[C:15]([C:18]3[NH:23][C:22]4[S:24][CH:25]=[C:26]([CH2:27][NH:28][S:29]([NH:32]C(=O)OCC5C=CC=CC=5)(=[O:31])=[O:30])[C:21]=4[S:20](=[O:44])(=[O:43])[N:19]=3)=[C:14]([OH:45])[C@H:13]3[C@@H:8]2[C@H:9]2[CH2:46][C@@H:12]3[CH2:11][CH2:10]2)=[CH:4][CH:3]=1>CO.[Pd]>[F:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:6][N:7]2[C:16](=[O:17])[C:15]([C:18]3[NH:23][C:22]4[S:24][CH:25]=[C:26]([CH2:27][NH:28][S:29]([NH2:32])(=[O:31])=[O:30])[C:21]=4[S:20](=[O:43])(=[O:44])[N:19]=3)=[C:14]([OH:45])[C@H:13]3[C@@H:8]2[C@H:9]2[CH2:46][C@@H:12]3[CH2:11][CH2:10]2)=[CH:47][CH:48]=1

Participants

4

Reactant 1

HCID 136395909benzyl (N-{3-[(1R,2S,7R,8S)-3-(4-fluoro-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-thieno[2,3-e][1,2,4]thiadiazin-7-ylmethyl}amino)sulfonylcarbamate

Product 1

HCID 136395908N-{3-[(1R,2S,7R,8S)-3-(4-fluoro-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-thieno[2,3-e][1,2,4]thiadiazin-7-ylmethyl}-sulfamideYield 88.2%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Procedure

To a solution of benzyl (N-{3-[(1R,2S,7R,8S)-3-(4-fluoro-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-thieno[2,3-e][1,2,4]thiadiazin-7-ylmethyl}amino)sulfonylcarbamate (120 mg, 0.17 mmol) in methanol (20 mL) was added 10% palladium on carbon (60 mg). The mixture was degassed and stirred under an atmosphere of hydrogen gas (balloon) overnight. The resulting mixture was filtered through a pad of Celite. The organic was concentrated in vacuo. The residue was purified via flash column chromatography (Teledyne Isco RediSep column; 0-3% methanol in dichloromethane) to afford the desired product, N-{3-[(1R,2S,7R,8S)-3-(4-fluoro-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-thieno[2,3-e][1,2,4]thiadiazin-7-ylmethyl}-sulfamide (89 mg, 0.15 mmol, 88%), as a white solid. 1H NMR (400 MHz, CDCl3) δ: 1.19-1.79 (6H, m), 2.57-2.58 (1H, m), 2.83-2.88 (2H, m), 3.49 (1H, d, J=9.6 Hz), 4.22 (1H, d, J=15.6 Hz), 4.48 (2H, d, J=6.4 Hz), 4.55 (2H, bs), 5.16 (1H, d, J=14.8 Hz), 5.29-5.32 (1H, m), 7.03-7.07 (3H, m), 7.19-7.22 (2H, m). LC-MS (ESI) calculated for C23H24FN5O6S3 581.66. found 582.2 [M+H+].

Workup

  1. customThe mixture was degassed
  2. filtrationThe resulting mixture was filtered through a pad of Celite
  3. concentrationThe organic was concentrated in vacuo
  4. customThe residue was purified via flash column chromatography (Teledyne Isco RediSep column; 0-3% methanol in dichloromethane)

Sources & evidence

ORD record
ord-2dc0008d5b1442acb0154bfef5ce4afe
Source dataset
uspto-grants-2012_07
Patent number
US08222404B2

Reaction notes

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