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 473220Notes

Reaction equation

HRID 473220 reaction equation
[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

Participants

3

Reactant 1

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

Product 1

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

Reagents, catalysts & solvents 1

HCID 18323598NaOH dioxaneSolvent

Procedure

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).

Workup

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

Sources & evidence

ORD record
ord-48d14cc8cd814b06a66bec3e3083486e
Source dataset
uspto-grants-2014_01
Patent number
US08633207B2

Reaction notes

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