Benzyl Alcohol → 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

HRID 421515Notes

Reaction equation

HRID 421515 reaction equation
Cl[S:2]([N:5]=[C:6]=[O:7])(=[O:4])=[O:3].[CH2:8]([OH:15])[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1.[NH2:16][CH2:17][C:18]1[C:26]2[S:25](=[O:28])(=[O:27])[N:24]=[C:23]([C:29]3[C:30](=[O:49])[N:31]([CH2:41][C:42]4[CH:47]=[CH:46][C:45]([F:48])=[CH:44][CH:43]=4)[C@@H:32]4[C@H:37]([C:38]=3[OH:39])[C@@H:36]3[CH2:40][C@H:33]4[CH2:34][CH2:35]3)[NH:22][C:21]=2[S:20][CH:19]=1.C(N(CC)CC)C>ClCCl>[F:48][C:45]1[CH:46]=[CH:47][C:42]([CH2:41][N:31]2[C:30](=[O:49])[C:29]([C:23]3[NH:22][C:21]4[S:20][CH:19]=[C:18]([CH2:17][NH:16][S:2]([NH:5][C:6](=[O:7])[O:15][CH2:8][C:9]5[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=5)(=[O:4])=[O:3])[C:26]=4[S:25](=[O:27])(=[O:28])[N:24]=3)=[C:38]([OH:39])[C@H:37]3[C@@H:32]2[C@H:33]2[CH2:40][C@@H:36]3[CH2:35][CH2:34]2)=[CH:43][CH:44]=1

Participants

6

Reactant 4

HCID 244Benzyl AlcoholHCID 8471TriethylamineHCID 70918Chlorosulfonyl isocyanateHCID 136395907(1R,2S,7R,8S)-5-(7-aminomethyl-1,1-dioxo-1,4-dihydro-1lambda6-thieno[2,3-e][1,2,4]thiadiazin-3-yl)-3-(4-fluoro-benzyl)-6-hydroxy-3-aza-tricyclo[6.2.1.02,7]undec-5-en-4-one

Product 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)sulfonylcarbamateYield 86%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Conditions

Temperature
25 °C

Procedure

To a solution of chlorosulfonylisocyanate (28 μL, 0.32 mmol) in dichloromethane (3 mL) was added benzyl alcohol (28 μL, 0.27 mmol). The reaction was stirred at 25° C. for 30 min. A solution of (1R,2S,7R,8S)-5-(7-aminomethyl-1,1-dioxo-1,4-dihydro-1λ6-thieno[2,3-e][1,2,4]thiadiazin-3-yl)-3-(4-fluoro-benzyl)-6-hydroxy-3-aza-tricyclo[6.2.1.02,7]undec-5-en-4-one (prepared as described in Example 33f; 0.10 g, 0.21 mmol) and triethylamine (125 μL, 0.90 mmol) in dichloromethane (3 mL) was then added to the above solution via cannula. The reaction was stirred at 25° C. for 1.5 h. The mixture was diluted with dichloromethane (10 mL) and washed with 1.0 M aqueous hydrochloric acid solution (10 mL). The organic was dried over magnesium sulfate, filtered and 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, 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 (0.13 g, 0.18 mmol, 86%), as a white solid. 1H NMR (400 MHz, CDCl3) δ: 1.19-1.77 (6H, m), 2.57-2.58 (1H, m), 2.83-2.88 (2H, m), 3.46 (1H, m), 4.22 (1H, d, J=15.6 Hz), 4.50 (2H, bs), 5.12-5.18 (3H, m), 6.06 (1H, bs), 7.02-7.07 (3H, m), 7.19-7.23 (2H, m), 7.33-7.39 (5H, m).

Workup

  1. stirringThe reaction was stirred at 25° C. for 1.5 h
  2. washwashed with 1.0 M aqueous hydrochloric acid solution (10 mL)
  3. dry with materialThe organic was dried over magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified via flash column chromatography (Teledyne Isco RediSep column; 0-3% methanol in dichloromethane)

Sources & evidence

ORD record
ord-bd72d1a65cd44d3091be2e38c7575f28
Source dataset
uspto-grants-2012_01
Patent number
US08097613B2

Reaction notes

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