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HRID548308

反应详情

EQUATION

反应方程式

HRID 548308 的结构方程式

REACTANTS

反应物

3
结构：Cl
HCID313

Hydrochloric Acid

ClH

结构：CC[O-].[Na+]
HCID2723922

Ethanol, sodium salt

C2H5NaO

结构：CCOC(=O)[C@@H]1[C@H]2CC[C@H](C2)[C@@H]1N(Cc1ccc(F)cc1)C(=O)CC1=NS(=O)(=O)c2cc(NS(C)(=O)=O)ccc2N1
HCID66674926

未命名化合物

PRODUCTS

生成物

1
结构：CS(=O)(=O)Nc1ccc2c(c1)S(=O)(=O)N=C(C1=C(O)[C@@H]3[C@H]4CC[C@H](C4)[C@@H]3N(Cc3ccc(F)cc3)C1=O)N2
HCID135565932

N-(3-((1R,2S,7R,8S)-3-((4-fluorophenyl)methyl)-6-hydroxy-4-oxo-3-azatricyclo (6.2.1.02,7)undec-5-en-5-yl)-1,1-dioxo-1,4-dihydro-1lambda6,2,4-benzothiadiazin-7- yl)methanesulfonamide

C25H25FN4O6S2

收率 68%

AUXILIARIES

试剂、催化剂与溶剂

2
结构：CCO
溶剂HCID702

Ethanol

C2H6O

2 次

结构：CCOC(C)=O
溶剂HCID8857

Ethyl acetate

C4H8O2

CONDITIONS

反应条件

温度
60 °C

PROCEDURE

实验过程

To a solution of the crude (1S,2R,3S,4R)-3-{(4-fluorobenzyl)-[2-(7-methanesulfonylamino-1,1-dioxo-1,4-dihydro-1λ6-benzo[1,2,4]thiadiazin-3-yl)-acetyl]-amino}-bicyclo[2.2.1]heptane-2-carboxylic acid ethyl ester in absolute ethanol (3 mL) was added a 21 wt. % solution of sodium ethoxide in ethanol (0.51 mL, 1.37 mmol). After stirring at 60° C. for 2 h, the mixture was diluted with ethyl acetate and acidified with 1.0 M aqueous hydrochloric acid solution to pH 1. The organic layer was separated and the aqueous layer was extracted with ethyl acetate (2×20 mL). The combined organic layer was dried over magnesium sulfate, filtered, and concentrated in vacuo. The crude mixture was purified by flash column chromatography (Teledyne Isco RediSep column; 0 to 100% ethyl acetate in hexanes) to afford the desired product, 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}-methanesulfonamide (131.5 mg, 0.235 mmol, 68% over two steps), as an off-white solid. 1H NMR (400 MHz, CD3OD) δ 1.28 (2H, d, J=11.0 Hz), 1.47 (1H, t, J=10.8 Hz), 1.57-1.74 (3H, m), 2.56 (1H, d, J=3.2 Hz), 2.75 (1H, d, J=2.3 Hz), 2.96 (1H, d, J=9.2 Hz), 3.02 (3H, s), 3.58 (1H, d, J=9.2 Hz), 4.42 (1H, d, J=15.5 Hz), 5.03 (1H, d, J=15.7 Hz), 7.04 (2H, t, J=8.5 Hz), 7.31 (2H, dd, J1=7.9 Hz, J2=5.5 Hz), 7.37 (1H, d, J=8.8 Hz), 7.54 (1H, dd, J1=8.3 Hz, J2=2.3 Hz), 7.69 (1H, d, J=2.3 Hz). LC-MS (ESI) calcd for C25H25FN4O6S2 560.12, found 561.4 [M+H+]. ee=98.5% [HPLC-analysis: Chiralpak AS-RH 2.1×150 mm, 5 micron at r.t., Solvent A-Solvent B (see table for gradient), 0.3 mL/min, 312 nm, t1=7.58 min (major), t2=8.95 min].

WORKUP

后处理

  1. customThe organic layer was separated
  2. extractionthe aqueous layer was extracted with ethyl acetate (2×20 mL)
  3. dry with materialThe combined organic layer was dried over magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe crude mixture was purified by flash column chromatography (Teledyne Isco RediSep column; 0 to 100% ethyl acetate in hexanes)