Hydrochloric Acid → HCID 178515396, compound

HRID 1751251Notes

Reaction equation

HRID 1751251 reaction equation
C(O[C:4]([C@H:6]1[C@@H:11]([N:12]([C:21](=[O:35])[CH2:22][C:23]2[NH:28][C:27]3[CH:29]=[CH:30][CH:31]=[CH:32][C:26]=3[S:25](=[O:34])(=[O:33])[N:24]=2)[CH2:13][C:14]2[CH:19]=[CH:18][C:17]([F:20])=[CH:16][CH:15]=2)[C@H:10]2[CH2:36][C@@H:7]1[CH2:8][CH2:9]2)=[O:5])C.[O-]CC.[Na+].Cl>C(O)C>[O:34]=[S:25]1(=[O:33])[C:26]2[CH:32]=[CH:31][CH:30]=[CH:29][C:27]=2[N:28]=[C:23]([C:22]2[C:21](=[O:35])[N:12]([CH2:13][C:14]3[CH:19]=[CH:18][C:17]([F:20])=[CH:16][CH:15]=3)[C@@H:11]3[C@H:6]([C:4]=2[OH:5])[C@@H:7]2[CH2:36][C@H:10]3[CH2:9][CH2:8]2)[NH:24]1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 2723922Sodium ethoxideHCID 66673836HCID 66673836, compound

Product 1

HCID 178515396HCID 178515396, compoundYield 62.1%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent2×

Conditions

Temperature
60 °C

Procedure

The crude (1S,2R,3S,4R)-3-[[2-(1,1-dioxo-1,4-dihydro-1λ6-benzo[1,2,4]thiadiazin-3-yl)-acetyl]-(4-fluoro-benzyl)-amino]-bicyclo[2.2.1]heptane-2-carboxylic acid ethyl ester was dissolved in ethanol (8 mL), and a 21 wt. % solution of sodium ethoxide in ethanol (1.6 mL, 4.2 mmol) was added into the above solution. The mixture was stirred at 60° C. for 4 h and allowed to cool down to 25° C. The mixture was poured into 0.5M aqueous hydrochloric acid solution (100 mL). The product started to precipitate and was collected by vacuum filtration. The precipitate was purified by flash column chromatography (Teledyne Isco RediSep column; 100% ethyl acetate) to afford the desired product, (1R,2S,7R,8S)-5-(1,1-dioxo-1,2-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 (0.242 g, 0.517 mmol, 62.1% over two steps), as a white solid. 1H NMR (400 MHz, DMSO-d6) δ: 1.16-1.22 (2H, m), 1.40-1.60 (4H, m), 2.51 (1H, bs), 2.64 (1H, d, J=2.1 Hz), 3.03 (1H, d, J=8.0 Hz), 3.54 (1H, d, J=9.3 Hz), 4.42 (1H, d, J=15.6 Hz), 4.97 (1H, d, J=15.7 Hz), 7.15 (2H, t, J=8.8 Hz), 7.33 (2H, dd, J1=8.0 Hz, J2=5.9 Hz), 7.45-7.53 (2H, m), 7.67-7.71 (1H, m), 7.85 (1H, d, J=7.9 Hz). LC-MS (ESI) calcd for C24H22FN3O4S 467.13, found 468.2 [M+H+]. Anal. calcd for C24H22FN3O4S: C, 61.66; H, 4.74; N, 8.99; found C, 61.96; H, 4.88; N, 8.99.

Workup

  1. temperatureto cool down to 25° C
  2. customto precipitate
  3. filtrationwas collected by vacuum filtration
  4. customThe precipitate was purified by flash column chromatography (Teledyne Isco RediSep column; 100% ethyl acetate)

Sources & evidence

ORD record
ord-0dad0dcb77be4715b871c2f93b93b4e0
Source dataset
uspto-grants-2015_10
Patent number
US09156832B2

Reaction notes

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