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Dimethylamine → 4-(2-Fluoro-4-hydroxymethyl-phenoxy)-2,2-dimethyl-2,3-dihydro-benzofuran-6-carboxylic acid (1-methyl-1H-pyrazol-3-yl)-amide

HRID 1177100
ノート
印刷プレビュー

反応式

HRID 1177100 の反応式
[CH3:1][NH:2][CH3:3].[BH3-]C#N.[Na+].[CH3:8][N:9]1[CH:13]=[CH:12][C:11]([NH:14][C:15]([C:17]2[CH:27]=[C:26]([O:28][C:29]3[CH:34]=[CH:33][C:32]([CH:35]=[O:36])=[CH:31][C:30]=3[F:37])[C:20]3[CH2:21][C:22]([CH3:25])([CH3:24])[O:23][C:19]=3[CH:18]=2)=[O:16])=[N:10]1>CO>[CH3:8][N:9]1[CH:13]=[CH:12][C:11]([NH:14][C:15]([C:17]2[CH:27]=[C:26]([O:28][C:29]3[CH:34]=[CH:33][C:32]([CH2:35][N:2]([CH3:3])[CH3:1])=[CH:31][C:30]=3[F:37])[C:20]3[CH2:21][C:22]([CH3:24])([CH3:25])[O:23][C:19]=3[CH:18]=2)=[O:16])=[N:10]1.[CH3:8][N:9]1[CH:13]=[CH:12][C:11]([NH:14][C:15]([C:17]2[CH:27]=[C:26]([O:28][C:29]3[CH:34]=[CH:33][C:32]([CH2:35][OH:36])=[CH:31][C:30]=3[F:37])[C:20]3[CH2:21][C:22]([CH3:25])([CH3:24])[O:23][C:19]=3[CH:18]=2)=[O:16])=[N:10]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

6

反応物 3

HCID 674Dimethylamine2 回HCID 5003444Sodium cyanoborohydride2 回HCID 595600834-(2-fluoro-4-formyl-phenoxy)-2,2-dimethyl-2,3-dihydro-benzofuran-6-carboxylic acid (1-methyl-1H-pyrazol-3-yl)-amide

生成物 2

HCID 595600364-(4-dimethylaminomethyl-2-fluoro-phenoxy)-2,2-dimethyl-2,3-dihydro-benzofuran-6-carboxylic acid(1-methyl-1H-pyrazol-3-yl)-amide収率 24%
HCID 59560258
4-(2-Fluoro-4-hydroxymethyl-phenoxy)-2,2-dimethyl-2,3-dihydro-benzofuran-6-carboxylic acid (1-methyl-1H-pyrazol-3-yl)-amide
収率 25%

試薬・触媒・溶媒 1

HCID 887Methanol溶媒

反応条件

温度
50 °C

実験手順

To dimethylamine (0.6 mL, 2.0 M, 1.0 mmol) in MeOH (5 mL) was added NaCNBH3 (31 mg, 0.49 mmol). The mixture was heated to 50° C. for 1 hr, and then 4-(2-fluoro-4-formyl-phenoxy)-2,2-dimethyl-2,3-dihydro-benzofuran-6-carboxylic acid (1-methyl-1H-pyrazol-3-yl)-amide (39a) (100 mg, 0.24 mmol) was added. The reaction mixture was heated to 50° C. for 1 hr. Additional NaCNBH3 (31 mg, 0.49 mmol) and dimethylamine (0.3 mL, 2.0 M, 0.5 mmol) were added to the reaction mixture. The mixture was heated at 50° C. for 1 hr, then concentrated and purified by reverse phase chromatograph to give 4-(4-dimethylaminomethyl-2-fluoro-phenoxy)-2,2-dimethyl-2,3-dihydro-benzofuran-6-carboxylic acid (1-methyl-1H-pyrazol-3-yl)-amide (26 mg, 24% yield) and 4-(2-Fluoro-4-hydroxymethyl-phenoxy)-2,2-dimethyl-2,3-dihydro-benzofuran-6-carboxylic acid (1-methyl-1H-pyrazol-3-yl)-amide (25 mg, 25% yield) as white solid.

後処理

  1. temperatureThe reaction mixture was heated to 50° C. for 1 hr
  2. temperatureThe mixture was heated at 50° C. for 1 hr
  3. concentrationconcentrated
  4. custompurified by reverse phase chromatograph

出典と根拠

ORDレコード
ord-e4dba46d89ab48abaf96588108104844
出典データセット
uspto-grants-2010_11
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US07842713B2

反応ノート

読み込み中…

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