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Sodium ethoxide → cis-N-{3-[1-(4-chloro-benzyl)-4-hydroxy-2-oxo-2,4a,5,6,7,7a-hexahydro-1H-[1]pyrindin-3-yl]-1,1-dioxo-1,4-dihydro-1lambda6-benzo[1,2,4]thiadiazin-7-yl}-methanesulfonamide

HRID 731385
ノート
印刷プレビュー

反応式

HRID 731385 の反応式
C([O:3][C:4]([CH:6]1[CH2:10][CH2:9][CH2:8][CH:7]1[N:11]([CH2:32][C:33]1[CH:38]=[CH:37][C:36]([Cl:39])=[CH:35][CH:34]=1)[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+]>C(O)C>[Cl:39][C:36]1[CH:37]=[CH:38][C:33]([CH2:32][N:11]2[C@@H:7]3[C@@H:6]([CH2:10][CH2:9][CH2:8]3)[C:4]([OH:3])=[C:13]([C:14]3[NH:19][C:18]4[CH:20]=[CH:21][C:22]([NH:24][S:25]([CH3:28])(=[O:26])=[O:27])=[CH:23][C:17]=4[S:16](=[O:30])(=[O:29])[N:15]=3)[C:12]2=[O:31])=[CH:34][CH:35]=1
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

4

反応物 2

HCID 2723922Sodium ethoxideHCID 576711922-{(4-Chloro-benzyl)-[2-(7-methanesulfonylamino-1,1-dioxo-1,4-dihydro-1lambda6-benzo[1,2,4]thiadiazin-3-yl)-acetyl]-amino}-cyclopentanecarboxylic acid ethyl ester

生成物 1

HCID 137194589cis-N-{3-[1-(4-chloro-benzyl)-4-hydroxy-2-oxo-2,4a,5,6,7,7a-hexahydro-1H-[1]pyrindin-3-yl]-1,1-dioxo-1,4-dihydro-1lambda6-benzo[1,2,4]thiadiazin-7-yl}-methanesulfonamide収率 26.2%

試薬・触媒・溶媒 1

HCID 702
Ethanol
溶媒
2 回

反応条件

温度
60 °C

実験手順

A solution of the crude 2-{(4-chloro-benzyl)-[2-(7-methanesulfonylamino-1,1-dioxo-1,4-dihydro-1λ6-benzo[1,2,4]thiadiazin-3-yl)-acetyl]-amino}-cyclopentanecarboxylic acid ethyl ester in ethanol (20 mL) was treated with a 21% w/w solution of sodium ethoxide in ethanol (0.648 g) and stirred for 16 h at 60° C. Upon cooling, the reaction mixture was then quenched with 1.0 M aqueous hydrochloric acid solution (20 mL) and extracted with ethyl acetate (2×50 mL). The combined organic layers were washed with saturated aqueous sodium bicarbonate solution, dried over sodium sulfate, filtered, and dried in vacuo. The residue was purified by prep-HPLC [Column ODS-A 5μ 100 Å, 150×21.2 mm, 5 micron, 50%-100% in 13.5 min @ 22 mL/min flow rate, 0.05% trifluoroacetic acid in acetonitrile/0.05% trifluoroacetic acid in water] to afford the desired product, cis-N-{3-[1-(4-chloro-benzyl)-4-hydroxy-2-oxo-2,4a,5,6,7,7a-hexahydro-1H-[1]pyrindin-3-yl]-1,1-dioxo-1,4-dihydro-1λ6-benzo[1,2,4]thiadiazin-7-yl}-methanesulfonamide (72.1 mg, 0.131 mmol, 26.2% over two steps), as a white solid. 1H NMR (400 MHz, DMSO-d6) δ: 1.44-1.62 (4H, m), 1.91-2.18 (3H, m), 3.06 (3H, s), 3.78-3.94 (1H, m), 4.39-4.62 (1H, m), 4.90 (1H, d, J=15.6 Hz), 7.35-7.64 (7H, m), 10.19 (1H, s). LC-MS (ESI) calcd for C23H23ClN4O6S2 550.07, found 551.4 [M+H+].

後処理

  1. temperatureUpon cooling
  2. customthe reaction mixture was then quenched with 1.0 M aqueous hydrochloric acid solution (20 mL)
  3. extractionextracted with ethyl acetate (2×50 mL)
  4. washThe combined organic layers were washed with saturated aqueous sodium bicarbonate solution
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. customdried in vacuo
  8. customThe residue was purified by prep-HPLC [Column ODS-A 5μ 100 Å, 150×21.2 mm, 5 micron, 50%-100% in 13.5 min @ 22 mL/min flow rate, 0.05% trifluoroacetic acid in acetonitrile/0.05% trifluoroacetic acid in water]

出典と根拠

ORDレコード
ord-f1e95964208544f2a775da20387136d6
出典データセット
uspto-grants-2009_09
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US07582626B2

反応ノート

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