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Hydrochloric Acid → N-[3-[(4aS,7aR)-1-(3,3-dimethylbutyl)-4-hydroxy-2-oxo-5,6,7,7a-tetrahydro-4aH-cyclopenta[b]pyridin-3-yl]-1,1-dioxo-4H-1$l^{6},2,4-benzothiadiazin-7-yl]methanesulfonamide

HRID 731288
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HRID 731288 반응식
C([O:3][C:4]([C@@H:6]1[CH2:10][CH2:9][CH2:8][C@@H:7]1[N:11]([CH2:32][CH2:33][C:34]([CH3:37])([CH3:36])[CH3:35])[C:12](=[O:31])[CH2:13][C:14]1[NH:19][C:18]2[CH:20]=[CH:21][C:22]([NH:24][S:25]([CH3:28])(=[O:27])=[O:26])=[CH:23][C:17]=2[S:16](=[O:30])(=[O:29])[N:15]=1)=O)C.[O-]CC.[Na+].Cl>C(O)C.C(OCC)(=O)C>[CH3:35][C:34]([CH3:37])([CH3:36])[CH2:33][CH2:32][N:11]1[C:12](=[O:31])[C:13]([C:14]2[NH:19][C:18]3[CH:20]=[CH:21][C:22]([NH:24][S:25]([CH3:28])(=[O:27])=[O:26])=[CH:23][C:17]=3[S:16](=[O:29])(=[O:30])[N:15]=2)=[C:4]([OH:3])[C@@H:6]2[C@H:7]1[CH2:8][CH2:9][CH2:10]2
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참가 물질

6

반응물 3

HCID 313Hydrochloric AcidHCID 2723922Sodium ethoxideHCID 69066044cis-2-{(3,3-Dimethylbutyl)-[2-(7-methanesulfonylamino-1,1-dioxo-1,4-dihydro-1lambda6-benzo[1,2,4]thiadiazin-3-yl)acetyl]amino}-cyclopentanecarboxylic acid ethyl ester

생성물 1

HCID 136117774N-[3-[(4aS,7aR)-1-(3,3-dimethylbutyl)-4-hydroxy-2-oxo-5,6,7,7a-tetrahydro-4aH-cyclopenta[b]pyridin-3-yl]-1,1-dioxo-4H-1$l^{6},2,4-benzothiadiazin-7-yl]methanesulfonamide수율 46%

시약·촉매·용매 2

HCID 702Ethanol용매2회HCID 8857Ethyl Acetate용매

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온도
60 °C

실험 절차

To a solution of cis-2-{(3,3-dimethylbutyl)-[2-(7-methanesulfonylamino-1,1-dioxo-1,4-dihydro-1λ6-benzo[1,2,4]thiadiazin-3-yl)acetyl]amino}-cyclopentanecarboxylic acid ethyl ester (125.8 mg, 0.226 mmol) in absolute ethanol (10 mL) was added a 21% w/w solution of sodium ethoxide in ethanol (0.84 mL, 2.25 mmol). After stirring at 60° C. for 4 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 layers were dried over anhydrous magnesium sulfate and concentrated in vacuo. The crude mixture was purified by flash column chromatography (Teledyne Isco RediSep Flash Column; 0-100% ethyl acetate in hexanes) to afford the desired product, cis-N-{3-[2-(3,3-dimethylbutyl)-5-hydroxy-3-oxo-2-aza-bicyclo[4.3.0]non-4-en-4-yl]-1,1-dioxo-1,4-dihydro-1λ6-benzo[1,2,4]thiadiazin-7-yl}-methanesulfonamide (52.7 mg, 0.103 mmol, 46%), as an off-white solid. 1H NMR (400 MHz, DMSO-d6) δ 0.94 (9H, s), 1.56-1.57 (5H, m), 2.08-2.15 (3H, m), 3.05 (3H, s), 3.17 (1H, bs), 3.34 (1H, bs), 3.64-3.72 (1H, m), 3.90 (1H, bs), 7.48-7.60 (3H, m), 10.17 (1H, bs). LC-MS (ESI) calcd for C22H30N4O6S2 510.16, found 511.4 [M+H+]. Anal. calcd for C22H30N4O6S2 0.3H2O: C, 51.20; H, 5.98; N, 10.86; S, 12.43, found C, 51.39; H, 5.81; N, 10.65; S, 12.26.

후처리

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

출처 및 근거

ORD 기록
ord-0be50f1d73624752a0f6f4c192e29ce1
출처 데이터셋
uspto-grants-2009_09
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US07582626B2

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