methyl 2-(difluoro(5-fluoropyridin-2-yl)methyl)-4-((5-methyl-1H-pyrazol-3-yl)amino)quinazoline-8-carboxylate → 2-(difluoro(5-fluoropyridin-2-yl)methyl)-4-((5-methyl-1H-pyrazol-3-yl)amino)quinazoline-8-carboxylic acid

HRID 473220ノート

反応式

HRID 473220 の反応式
[F:1][C:2]([F:31])([C:24]1[CH:29]=[CH:28][C:27]([F:30])=[CH:26][N:25]=1)[C:3]1[N:12]=[C:11]([NH:13][C:14]2[CH:18]=[C:17]([CH3:19])[NH:16][N:15]=2)[C:10]2[C:5](=[C:6]([C:20]([O:22]C)=[O:21])[CH:7]=[CH:8][CH:9]=2)[N:4]=1>[OH-].[Na+].O1CCOCC1>[F:31][C:2]([F:1])([C:24]1[CH:29]=[CH:28][C:27]([F:30])=[CH:26][N:25]=1)[C:3]1[N:12]=[C:11]([NH:13][C:14]2[CH:18]=[C:17]([CH3:19])[NH:16][N:15]=2)[C:10]2[C:5](=[C:6]([C:20]([OH:22])=[O:21])[CH:7]=[CH:8][CH:9]=2)[N:4]=1

参加物

3

反応物 1

HCID 56848866methyl 2-(difluoro(5-fluoropyridin-2-yl)methyl)-4-((5-methyl-1H-pyrazol-3-yl)amino)quinazoline-8-carboxylate

生成物 1

HCID 568489252-(difluoro(5-fluoropyridin-2-yl)methyl)-4-((5-methyl-1H-pyrazol-3-yl)amino)quinazoline-8-carboxylic acid収率 93.4%

試薬・触媒・溶媒 1

HCID 18323598NaOH dioxane溶媒

実験手順

A solution of methyl 2-(difluoro(5-fluoropyridin-2-yl)methyl)-4-((5-methyl-1H-pyrazol-3-yl)amino)quinazoline-8-carboxylate (26.7 g, 62.3 mmol) in 1:1 3N NaOH/dioxane (200 mL) was stirred at rt for 2 h. The mixture was concentrated under reduced pressure, and the resulting aqueous solution was acidified with 3N HCl. The resulting precipitate was collected by filtration, washed with water, and dried in air to afford 2-(difluoro(5-fluoropyridin-2-yl)methyl)-4-((5-methyl-1H-pyrazol-3-yl)amino)quinazoline-8-carboxylic acid as a solid (24.1 g, 93%). LC-MS (ESI) m/z 415.6 (M+H). 1H NMR (500 MHz, DMSO-d6) δ 15.61 (1H, br s), 12.39 (1H, br s), 11.41 (1H, br s), 9.00 (1H, d, J=8.2 Hz), 8.71 (1H, s), 8.59 (1H, d, J=7.36 Hz), 8.09-8.03 (2H, m), 7.83 (1H, t, J=7.86 Hz), 6.07 (1H, s), 2.20 (3H, s).

後処理

  1. concentrationThe mixture was concentrated under reduced pressure
  2. filtrationThe resulting precipitate was collected by filtration
  3. washwashed with water
  4. customdried in air

出典と根拠

ORDレコード
ord-48d14cc8cd814b06a66bec3e3083486e
出典データセット
uspto-grants-2014_01
特許番号
US08633207B2

反応ノート

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