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 473220노트

반응식

HRID 473220 반응식
[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

참가 물질

3

반응물 1

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

생성물 1

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

시약·촉매·용매 1

HCID 18323598NaOH dioxane용매

실험 절차

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).

후처리

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

출처 및 근거

ORD 기록
ord-48d14cc8cd814b06a66bec3e3083486e
출처 데이터셋
uspto-grants-2014_01
특허 번호
US08633207B2

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