Hydrochloric Acid → 2-({3-[4-hydroxy-1-(isobutylamino)-2-oxo-1,2-dihydroquinolin-3-yl]-1,1-dioxido-4H-1,2,4-benzothiadiazin-7-yl}oxy)butanamide

HRID 601353ノート

反応式

HRID 601353 の反応式
[OH:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[N:5]([NH:12][CH2:13][CH:14]([CH3:16])[CH3:15])[C:4](=[O:17])[C:3]=1[C:18]1[NH:23][C:22]2[CH:24]=[CH:25][C:26]([OH:28])=[CH:27][C:21]=2[S:20](=[O:30])(=[O:29])[N:19]=1.Cl[CH:32]([CH2:36][CH3:37])[C:33]([NH2:35])=[O:34].C(=O)([O-])[O-].[Cs+].[Cs+].Cl>CN(C)C=O.[I-].C([N+](CCCC)(CCCC)CCCC)CCC>[OH:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[N:5]([NH:12][CH2:13][CH:14]([CH3:15])[CH3:16])[C:4](=[O:17])[C:3]=1[C:18]1[NH:23][C:22]2[CH:24]=[CH:25][C:26]([O:28][CH:32]([CH2:36][CH3:37])[C:33]([NH2:35])=[O:34])=[CH:27][C:21]=2[S:20](=[O:29])(=[O:30])[N:19]=1

参加物

7

反応物 4

HCID 313Hydrochloric AcidHCID 10796Cesium carbonateHCID 3449692-ChlorobutyramideHCID 1363584044-hydroxy-3-(7-hydroxy-1,1-dioxido-4H-1,2,4-benzothiadiazin-3-yl)-1-(isobutylamino)quinolin-2(1H)-one

生成物 1

HCID 1363584952-({3-[4-hydroxy-1-(isobutylamino)-2-oxo-1,2-dihydroquinolin-3-yl]-1,1-dioxido-4H-1,2,4-benzothiadiazin-7-yl}oxy)butanamide収率 100.1%

試薬・触媒・溶媒 2

HCID 67553Tetrabutylammonium Iodide触媒HCID 6228Dimethylformamide溶媒

反応条件

温度
25 °C

実験手順

To a solution of the product of Example 321C (20 mg, 0.0467 mmol) in N,N-dimethylformamide (2 mL) was added 2-chlorobutyramide (8.5 mg, 0.070 mmol), tetra-n-butylammonium iodide (1.7 mg, 0.0047 mmol) and cesium carbonate (61 mg, 0.187 mmol). The mixture was stirred at 25° C. for 18 hours, then heated to 80° C. for 3 hours. After cooling to 25° C., 1N aqueous hydrochloric acid (10 mL) was added and the mixture extracted with ethyl acetate (10 mL). The resulting organic layer was separated and dried over magnesium sulfate, filtered, and concentrated under reduced pressure to provide the title compound (24 mg, 100%). The sodium salt of the title compound was prepared according to the procedure of Example 1D. MS (ESI−) m/z 512 (M−Na)−. 1H NMR (300 MHz, DMSO-d6) δ 0.99 (t, J=7.7 Hz, 3H), 1.03 (d, J=6.3 Hz, 6H), 1.83 (m, 3H), 2.50 (m, 1H), 2.75 (m, 1H), 4.46 (m, 1H), 5.94 (m, 1H), 7.08 (m, 2H), 7.17 (m, 1H), 7.23 (m, 1H), 7.32 (s, 1H), 7.58 (m, 2H), 7.64 (s, 1H), 8.07 (d, J=7.8 Hz, 1H), 16.23 (bs, 1H).

後処理

  1. temperatureheated to 80° C. for 3 hours
  2. temperatureAfter cooling to 25° C.
  3. extractionthe mixture extracted with ethyl acetate (10 mL)
  4. customThe resulting organic layer was separated
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure

出典と根拠

ORDレコード
ord-43a7d4795e4f45c2aa2c3bea24c5cae3
出典データセット
uspto-grants-2011_03
特許番号
US07902203B2

反応ノート

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