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Triethylamine → 5-(3-{(5-fluoro-8-methoxy-2,3-dihydrobenzo[1,4]dioxin-6-yl)-[4-(5-methyl-[1,2,4]oxadiazol-3-yl)phenylamino]methyl}-5-oxo-4,5-dihydro-[1,2,4]triazol-1-yl)-1H-pyrazole-4-carboxylic acid ethyl ester

HRID 1161530
ノート
印刷プレビュー

反応式

HRID 1161530 の反応式
Cl.Cl.[CH2:3]([O:5][C:6]([C:8]1[C:9]([NH:13][NH2:14])=[N:10][NH:11][CH:12]=1)=[O:7])[CH3:4].C[O:16][C:17](=O)[N:18]=[C:19](SC)[C:20]([C:34]1[CH:43]=[C:42]([O:44][CH3:45])[C:37]2[O:38][CH2:39][CH2:40][O:41][C:36]=2[C:35]=1[F:46])=[N:21][C:22]1[CH:27]=[CH:26][C:25]([C:28]2[N:32]=[C:31]([CH3:33])[O:30][N:29]=2)=[CH:24][CH:23]=1.C(N(CC)CC)C>CN(C=O)C>[CH2:3]([O:5][C:6]([C:8]1[CH:12]=[N:11][NH:10][C:9]=1[N:13]1[C:17](=[O:16])[NH:18][C:19]([CH:20]([C:34]2[CH:43]=[C:42]([O:44][CH3:45])[C:37]3[O:38][CH2:39][CH2:40][O:41][C:36]=3[C:35]=2[F:46])[NH:21][C:22]2[CH:27]=[CH:26][C:25]([C:28]3[N:32]=[C:31]([CH3:33])[O:30][N:29]=3)=[CH:24][CH:23]=2)=[N:14]1)=[O:7])[CH3:4]
参加物実験手順後処理出典と根拠反応ノート

参加物

5

反応物 3

HCID 8471TriethylamineHCID 72312813[2-(5-Fluoro-8-methoxy-2,3-dihydrobenzo[1,4]dioxin-6-yl)-2-[4-(5-methyl-[1,2,4]oxadiazol-3-yl)phenylimino]-1-methylsulfanylethylidene]carbamic acid methyl esterHCID 178469938HCID 178469938、化合物

生成物 1

HCID 1359821585-(3-{(5-fluoro-8-methoxy-2,3-dihydrobenzo[1,4]dioxin-6-yl)-[4-(5-methyl-[1,2,4]oxadiazol-3-yl)phenylamino]methyl}-5-oxo-4,5-dihydro-[1,2,4]triazol-1-yl)-1H-pyrazole-4-carboxylic acid ethyl ester
収率 54.2%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

A solution of 62 mg of 3-hydrazino-1H-pyrazole-4-carboxylic acid ethyl ester bishydrochloride (Example (157b)), 106 mg of [2-(5-fluoro-8-methoxy-2,3-dihydrobenzo[1,4]dioxin-6-yl)-2-[4-(5-methyl-[1,2,4]oxadiazol-3-yl)phenylimino]-1-methylsulfanylethylidene]carbamic acid methyl ester (Example 41d) and 88 μl of triethylamine in 5 ml of DMF was heated at 85° C. for 15 hours under a nitrogen atmosphere with stirring. After cooling the reaction mixture to room temperature, the solvent was removed under reduced pressure. The residue was dissolved in 8 ml of methanol, and then 133 mg of sodium cyanotrihydroborate, 49 μl of acetic acid and 0.5 g of MS3A were added and the mixture was stirred at room temperature for 20 hours. Next, 100 ml of ethyl acetate and 50 ml of water were added, and the organic layer was washed with 50 ml of water and 50 ml of saturated brine in that order and then dried over anhydrous magnesium sulfate. The desiccating agent was filtered off, the filtrate was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (ethyl acetate-methanol) to give the title compound (68 mg) as a light green solid.

後処理

  1. customthe solvent was removed under reduced pressure
  2. dissolutionThe residue was dissolved in 8 ml of methanol
  3. addition133 mg of sodium cyanotrihydroborate, 49 μl of acetic acid and 0.5 g of MS3A were added
  4. stirringthe mixture was stirred at room temperature for 20 hours
  5. additionNext, 100 ml of ethyl acetate and 50 ml of water were added
  6. washthe organic layer was washed with 50 ml of water and 50 ml of saturated brine in that order
  7. dry with materialdried over anhydrous magnesium sulfate
  8. filtrationThe desiccating agent was filtered off
  9. concentrationthe filtrate was concentrated under reduced pressure
  10. customthe residue was purified by silica gel column chromatography (ethyl acetate-methanol)

出典と根拠

ORDレコード
ord-ef3480177f254eb9bd0349ca73db6920
出典データセット
uspto-grants-2010_10
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US07816522B2

反応ノート

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