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-benzo[1,2,4]thiadiazin-7-yl}-sulfamoyl]carbamate → (1R,2S,7R,8S)-N-{3-[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 benzo[1,2,4]thiadiazin-7-yl}-sulfamide

HRID 424255Notes

Reaction equation

HRID 424255 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[CH:24]=[CH:25][C:26]([NH:28][S:29]([NH:32]C(=O)OCC5C=CC=CC=5)(=[O:31])=[O:30])=[CH:27][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>[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[CH:24]=[CH:25][C:26]([NH:28][S:29]([NH2:32])(=[O:31])=[O:30])=[CH:27][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:4][CH:3]=1

Participants

3

Reactant 1

HCID 136404888benzyl [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-benzo[1,2,4]thiadiazin-7-yl}-sulfamoyl]carbamate

Product 1

HCID 136402487(1R,2S,7R,8S)-N-{3-[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 benzo[1,2,4]thiadiazin-7-yl}-sulfamideYield 58.7%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
25 °C

Procedure

The crude 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-benzo[1,2,4]thiadiazin-7-yl}-sulfamoyl]carbamate was dissolved in methanol (5 mL) and the mixture was degassed and backfilled with nitrogen (3×). Palladium on carbon (10% dry, 180 mg) was added and the mixture was degassed and backfilled with hydrogen gas via balloon. The mixture was stirred at 25° C. for 16 h. The mixture was passed through a plug of Celite and the filtrate was concentrated in vacuo to afford the crude product, which was further purified by prep-HPLC [Column Luna 5μ C18 (2) 100 Å AXIA 150×21.2 mm, 5 micron, 30%-95% in 7 min @ 30 mL/min flow rate, 0.05% trifluoroacetic acid in acetonitrile/0.05% trifluoroacetic acid in water] to afford the desired product, (1R,2S,7R,8S)—N-{3-[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-benzo[1,2,4]thiadiazin-7-yl}-sulfamide (55.7 mg, 0.099 mmol, 58.7% over two steps), as a white solid. 1H NMR (400 MHz, DMSO-d6) δ: 1.19-1.24 (2H, m), 1.40-1.60 (4H, m), 2.51-2.54 (1H, m), 2.64-2.65 (1H, m), 3.04 (1H, d, J=9.3 Hz), 3.53 (1H, d, J=9.3 Hz), 4.42 (1H, d, J=15.7 Hz), 4.96 (1H, d, J=15.6 Hz), 7.15 (2H, m), 7.31-7.34 (H, m), 7.43 (1H, dd, J1=9.4 Hz, J2=2.3 Hz), 7.51-7.55 (2H, m), 9.96 (1H, s). LC-MS (ESI) calcd for C24H24FN5O6S 561.12, found 562.5 [M+H+]. Anal. calcd for C24H24FN5O6S.0.5H2O: C, 50.51; H, 4.42; N, 12.27; found: C, 50.42, H, 4.35; N, 11.90.

Workup

  1. customthe mixture was degassed
  2. additionPalladium on carbon (10% dry, 180 mg) was added
  3. customthe mixture was degassed
  4. concentrationthe filtrate was concentrated in vacuo
  5. customto afford the crude product, which
  6. customwas further purified by prep-HPLC [Column Luna 5μ C18 (2) 100 Å AXIA 150×21.2 mm, 5 micron, 30%-95% in 7 min

Sources & evidence

ORD record
ord-0390249820294ccd840bcdcfe6cf41d5
Source dataset
uspto-grants-2012_01
Patent number
US08101800B2

Reaction notes

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