(1R,2S,7R,8S)-5-(7-azido-1,1-dioxo-1,4-dihydro-1lambda6-benzo[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 → (1R,2S,7R,8S)-5-(7-amino-1,1-dioxo-1,4-dihydro-1lambda6-benzo[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

HRID 1751255Notes

Reaction equation

HRID 1751255 reaction equation
[N:1]([C:4]1[CH:36]=[CH:35][C:7]2[NH:8][C:9]([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)=[N:10][S:11](=[O:13])(=[O:12])[C:6]=2[CH:5]=1)=[N+]=[N-]>CO.C(OCC)(=O)C.[Pd]>[NH2:1][C:4]1[CH:36]=[CH:35][C:7]2[NH:8][C:9]([C:14]3[C:15](=[O:34])[N:16]([CH2:26][C:27]4[CH:28]=[CH:29][C:30]([F:33])=[CH:31][CH:32]=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)=[N:10][S:11](=[O:12])(=[O:13])[C:6]=2[CH:5]=1

Participants

5

Reactant 1

HCID 136404886(1R,2S,7R,8S)-5-(7-azido-1,1-dioxo-1,4-dihydro-1lambda6-benzo[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 136402488(1R,2S,7R,8S)-5-(7-amino-1,1-dioxo-1,4-dihydro-1lambda6-benzo[1,2,4]thiadiazin-3-yl)-3-(4-fluoro-benzyl)-6-hydroxy-3-aza-tricyclo[6.2.1.02,7]undec-5-en-4-oneYield 48.2%

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 887MethanolSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
25 °C

Procedure

(1R,2S,7R,8S)-5-(7-Azido-1,1-dioxo-1,4-dihydro-1λ6-benzo[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 (0.348 g, 0.684 mmol) was dissolved in a 1:1 mixture if methanol and ethyl acetate (15 mL) at 25° C. Palladium on carbon (0.40 g, 5%, “wet”) was added, resulting in a black suspension. The reaction was maintained under a hydrogen atmosphere (balloon) at 25° C. for 6 h, and then was filtered through Celite. The Celite was washed with ethyl acetate (2×30 mL) and the filtrate was concentrated in vacuo. The residue was purified by flash column chromatography (Teledyne Isco RediSep column; 50 to 100% ethyl acetate in hexanes) to afford the desired product, (1R,2S,7R,8S)-5-(7-amino-1,1-dioxo-1,4-dihydro-1λ6-benzo[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 (0.159 g, 0.330 mmol, 48%), as a pale yellow solid. 1H NMR (400 MHz, CDCl3) δ: 1.08-1.19 (3H, m), 1.40-1.57 (3H, m), 2.99 (1H, d, J=7.2 Hz), 3.31 (3H, s), 3.36-3.37 (1H, m), 3.50 (1H, d, J=7.8 Hz), 4.39 (1H, d, J=14.6 Hz), 4.93 (1H, d, J=14.5 Hz), 6.86-6.91 (3H, m), 7.13-7.15 (2H, m), 7.21 (1H, d, J=8.8 Hz), 7.30 (2H, bs), 13.79 (1H, s). LC-MS (ESI) calcd for C24H23FN4O4S 482.14, found 483.4 [M+H+].

Workup

  1. customresulting in a black suspension
  2. filtrationwas filtered through Celite
  3. washThe Celite was washed with ethyl acetate (2×30 mL)
  4. concentrationthe filtrate was concentrated in vacuo
  5. customThe residue was purified by flash column chromatography (Teledyne Isco RediSep column; 50 to 100% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-4326fe72fa5a457192f30439b4a9fe41
Source dataset
uspto-grants-2015_10
Patent number
US09156832B2

Reaction notes

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