Triethylamine → cyclopropanesulfonic acid {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}-amide

HRID 1516029Notes

Reaction equation

HRID 1516029 reaction equation
[NH2:1][CH2:2][C:3]1[C:11]2[S:10](=[O:13])(=[O:12])[N:9]=[C:8]([C:14]3[C:15](=[O:34])[N:16]([CH2:26][C:27]4[CH:32]=[CH:31][C:30]([F:33])=[CH:29][CH:28]=4)[C@@H:17]4[C@H:22]([C:23]=3[OH:24])[C@@H:21]3[CH2:25][C@H:18]4[CH2:19][CH2:20]3)[NH:7][C:6]=2[S:5][CH:4]=1.C(N(CC)CC)C.[CH:42]1([S:45](Cl)(=[O:47])=[O:46])[CH2:44][CH2:43]1>ClCCl>[F:33][C:30]1[CH:29]=[CH:28][C:27]([CH2:26][N:16]2[C:15](=[O:34])[C:14]([C:8]3[NH:7][C:6]4[S:5][CH:4]=[C:3]([CH2:2][NH:1][S:45]([CH:42]5[CH2:44][CH2:43]5)(=[O:47])=[O:46])[C:11]=4[S:10](=[O:12])(=[O:13])[N:9]=3)=[C:23]([OH:24])[C@H:22]3[C@@H:17]2[C@H:18]2[CH2:25][C@@H:21]3[CH2:20][CH2:19]2)=[CH:32][CH:31]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 2760919Cyclopropanesulfonyl chlorideHCID 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 135936725cyclopropanesulfonic acid {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}-amideYield 85%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To 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 (0.10 g, 0.20 mmol) in dichloromethane (3 mL) at 0° C. was added triethylamine (56 μl, 0.40 mmol) and cyclopropanesulfonyl chloride (23 μl, 0.22 mmol). The reaction was stirred at 0° C. for 30 min, then at 25° C. for 2 h. The reaction was quenched with water (10 mL). The resulting mixture was extracted with ethyl acetate (3×10 mL). The organic layers were combined, dried over magnesium sulfate, filtered and concentrated in vacuo. The residue was purified via flash column chromatography (Teledyne Isco RediSep column; 0-1% methanol in dichloromethane) to afford the desired product, cyclopropanesulfonic acid {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}-amide (0.10 g, 0.17 mmol, 84%), as a white solid. 1H NMR (400 MHz, CDCl3) δ: 1.15-1.78 (10H, m), 2.32-2.38 (1H, m), 2.56-2.58 (1H, m), 2.84-2.88 (2H, m), 3.48 (1H, d, J=9.2 Hz), 4.21 (1H, d, J=15.6 Hz), 4.51 (2H, d, J=6.4 Hz), 5.15 (1H, d, J=14.8 Hz), 5.35 (1H, t, J=6.4 Hz), 7.02-7.07 (3H, m), 7.19-7.22 (2H, m). LC-MS (ESI) calculated for C26H27FN4O6S3 606.71. found 607.2 [M+H+].

Workup

  1. waitat 25° C. for 2 h
  2. customThe reaction was quenched with water (10 mL)
  3. extractionThe resulting mixture was extracted with ethyl acetate (3×10 mL)
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified via flash column chromatography (Teledyne Isco RediSep column; 0-1% methanol in dichloromethane)

Sources & evidence

ORD record
ord-59d38774ce90432a859e138d064d098f
Source dataset
uspto-grants-2012_07
Patent number
US08222404B2

Reaction notes

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