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4-Methylmorpholine → N-[3-[1-[(4-fluorophenyl)methyl]-4-hydroxy-3-(3-methylbut-2-enyl)-6-oxo-2,3-dihydropyridin-5-yl]-1,1-dioxo-4H-1$l^{6},2,4-benzothiadiazin-7-yl]methanesulfonamide

HRID 1172382
ノート
印刷プレビュー

反応式

HRID 1172382 の反応式
C(O[C:4](=[O:21])[CH:5]([CH2:11][NH:12][CH2:13][C:14]1[CH:19]=[CH:18][C:17]([F:20])=[CH:16][CH:15]=1)[CH2:6][CH:7]=[C:8]([CH3:10])[CH3:9])C.[CH3:22][S:23]([NH:26][C:27]1[CH:42]=[CH:41][C:30]2[NH:31][C:32]([CH2:37][C:38](O)=[O:39])=[N:33][S:34](=[O:36])(=[O:35])[C:29]=2[CH:28]=1)(=[O:25])=[O:24].Cl.CN(C)CCCN=C=NCC.CN1CCOCC1.[H-].[Na+]>CN(C)C=O.Cl>[F:20][C:17]1[CH:16]=[CH:15][C:14]([CH2:13][N:12]2[CH2:11][CH:5]([CH2:6][CH:7]=[C:8]([CH3:9])[CH3:10])[C:4]([OH:21])=[C:37]([C:32]3[NH:31][C:30]4[CH:41]=[CH:42][C:27]([NH:26][S:23]([CH3:22])(=[O:25])=[O:24])=[CH:28][C:29]=4[S:34](=[O:35])(=[O:36])[N:33]=3)[C:38]2=[O:39])=[CH:19][CH:18]=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

8

反応物 5

HCID 79724-MethylmorpholineHCID 24758Sodium hydrideHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 248585392H-1,2,4-Benzothiadiazine-3-acetic acid, 7-[(methylsulfonyl)amino]-, 1,1-dioxideHCID 576065982-[(4-Fluoro-benzylamino)-methyl]-5-methyl-hex-4-enoic acid ethyl ester

生成物 1

HCID 135949494
N-[3-[1-[(4-fluorophenyl)methyl]-4-hydroxy-3-(3-methylbut-2-enyl)-6-oxo-2,3-dihydropyridin-5-yl]-1,1-dioxo-4H-1$l^{6},2,4-benzothiadiazin-7-yl]methanesulfonamide
収率 46.4%

試薬・触媒・溶媒 2

HCID 313Hydrochloric Acid溶媒HCID 6228Dimethylformamide溶媒

反応条件

温度
25 °C

実験手順

A solution of 2-[(4-fluoro-benzylamino)-methyl]-5-methyl-hex-4-enoic acid ethyl ester (102 mg, 0.35 mmol), (7-methanesulfonylamino-1,1-dioxo-1,4-dihydro-1λ6-benzo[1,2,4]thiadiazin-3-yl)-acetic acid (115 mg, 0.345 mmol), and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (69 mg, 0.36 mmol) in anhydrous N,N-dimethylformamide (5 mL) was treated with N-methylmorpholine. The reaction was stirred for 1 h at 25° C., diluted with a 1.0 M aqueous hydrochloric acid solution (20 mL), and extracted with ethyl acetate (3×50 mL). The combined organic layers were dried over magnesium sulfate, filtered, and concentrated in vacuo. The residue was dissolved in ethanol (6 mL) and treated with a 60% oil dispersion of sodium hydride (41 mg, 1.74 mmol). The reaction was heated at 70° C. for 1 h, allowed to cool to 25° C., and quenched with a 1.0 M aqueous hydrochloric acid solution (50 mL). The resulting mixture was extracted with ethyl acetate (3×50 mL), and the combined organic layers were dried over magnesium sulfate, filtered, and concentrated in vacuo. The crude oil was purified by flash column chromatography (ISCO RediSep column, 10 to 80% ethyl acetate in hexanes) to give N-{3-[1-(4-fluoro-benzyl)-4-hydroxy-5-(3-methyl-but-2-enyl)-2-oxo-1,2,5,6-tetrahydro-pyridin-3-yl]-1,1-dioxo-1,4-dihydro-1λ6-benzo[1,2,4]thiadiazin-7-yl}-methanesulfonamide (90 mg, 46%) as a light yellow solid. 1H NMR (400 MHz, CDCl3) δ: 1.54 (s, 3H), 1.69 (s, 3H), 2.15-2.23 (m, 1H), 2.39-2.44 (m, 1H), 2.60-2.66 (m, 1H), 3.06 (s, 3H), 3.19 (dd, 1H, J1=13.1 Hz, J2=4.3 Hz), 3.45 (dd, 1H, J1=12.4 Hz, J2=5.4 Hz), 4.61 (s, 2H), 4.89 (t, 3H, J=6.6 Hz), 7.05 (t, 2H, J=8.5 Hz), 7.23-7.28 (m, 3H), 7.63-7.66 (m, 1H), 7.69 (d, 1H, J=2.2 Hz). LC-MS (ESI) calculated for C25H27FN4O6S2: 562.6, found 563.4 [M+H+].

後処理

  1. extractionextracted with ethyl acetate (3×50 mL)
  2. dry with materialThe combined organic layers were dried over magnesium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. dissolutionThe residue was dissolved in ethanol (6 mL)
  6. temperatureThe reaction was heated at 70° C. for 1 h
  7. temperatureto cool to 25° C.
  8. customquenched with a 1.0 M aqueous hydrochloric acid solution (50 mL)
  9. extractionThe resulting mixture was extracted with ethyl acetate (3×50 mL)
  10. dry with materialthe combined organic layers were dried over magnesium sulfate
  11. filtrationfiltered
  12. concentrationconcentrated in vacuo
  13. customThe crude oil was purified by flash column chromatography (ISCO RediSep column, 10 to 80% ethyl acetate in hexanes)

出典と根拠

ORDレコード
ord-91e7310a7d4c4271a325f57ada2de897
出典データセット
uspto-grants-2010_11
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US07834009B2

反応ノート

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