Sodium Carbonate → N-(5-(2-aminopyrimidin-4-yl)-pyridin-3-yl)-5,7-difluoro-3-methyl-2-(4-methylpyridin-2-yl)quinolin-4-amine

HRID 1431602ノート

反応式

HRID 1431602 の反応式
[F:1][C:2]1[CH:11]=[C:10]([F:12])[CH:9]=[C:8]2[C:3]=1[C:4]([NH:21][C:22]1[CH:23]=[C:24](B(O)O)[CH:25]=[N:26][CH:27]=1)=[C:5]([CH3:20])[C:6]([C:13]1[CH:18]=[C:17]([CH3:19])[CH:16]=[CH:15][N:14]=1)=[N:7]2.[NH2:31][C:32]1[N:37]=[C:36](Cl)[CH:35]=[CH:34][N:33]=1.C(=O)([O-])[O-].[Na+].[Na+].O1CCOCC1>C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.Cl[Pd]Cl.O>[NH2:31][C:32]1[N:37]=[C:36]([C:24]2[CH:23]=[C:22]([NH:21][C:4]3[C:3]4[C:8](=[CH:9][C:10]([F:12])=[CH:11][C:2]=4[F:1])[N:7]=[C:6]([C:13]4[CH:18]=[C:17]([CH3:19])[CH:16]=[CH:15][N:14]=4)[C:5]=3[CH3:20])[CH:27]=[N:26][CH:25]=2)[CH:35]=[CH:34][N:33]=1

参加物

7

反応物 4

HCID 10340Sodium CarbonateHCID 312751,4-DioxaneHCID 2233322-Amino-4-chloropyrimidineHCID 596313385-(5,7-Difluoro-3-methyl-2-(4-methylpyridin-2-yl)quinolin-4-ylamino)pyridin-3-ylboronic acid

生成物 1

HCID 50907185N-(5-(2-aminopyrimidin-4-yl)-pyridin-3-yl)-5,7-difluoro-3-methyl-2-(4-methylpyridin-2-yl)quinolin-4-amine

試薬・触媒・溶媒 2

HCID 6102075Dichlorobis(triphenylphosphine)palladium触媒HCID 962Water溶媒

反応条件

温度
95 °C

実験手順

A screw-cap vial was charged with 5-(5,7-difluoro-3-methyl-2-(4-methylpyridin-2-yl)quinolin-4-ylamino)pyridin-3-ylboronic acid (200 mg, 0.49 mmol), 2-amino-4-chloropyrimidine (63.8 mg, 0.49 mmol), bis(triphenylphosphine)palladium (II) chloride (34.6 mg, 0.049 mmol), sodium carbonate (157 mg, 1.48 mmol), 1,4-dioxane (4 mL), and water (1 mL). The solution was stirred at 95° C. for 30 min, and then cooled to rt. The product was extracted with EtOAc and DCM, and the combined organic layer was dried over magnesium sulfate and cond. The crude material was purified by flash-chromatography (basic alumina, 0-10% MeOH in DCM, then recrystallized in MeOH to afford N-(5-(2-aminopyrimidin-4-yl)-pyridin-3-yl)-5,7-difluoro-3-methyl-2-(4-methylpyridin-2-yl)quinolin-4-amine. Mass Spectrum (ESI) m/e=456.0 (M+1). 1H NMR (400 MHz, DMSO-d6) δ ppm 8.78 (1H, s), 8.63 (1H, d, J=1.8 Hz), 8.56 (1H, d), 8.31 (1H, d, J=5.3 Hz), 8.13 (1H, d), 7.75 (1H, s), 7.70 (1H, m), 7.60 (1H, m), 7.49 (1H, m), 7.35 (1H, m), 7.09 (1H, s), 6.68 (2H, s), 2.45 (3H, s), 2.20 (3H, s).

後処理

  1. temperaturecooled to rt
  2. extractionThe product was extracted with EtOAc and DCM
  3. dry with materialthe combined organic layer was dried over magnesium sulfate and cond
  4. customThe crude material was purified by flash-chromatography (basic alumina, 0-10% MeOH in DCM
  5. customrecrystallized in MeOH

出典と根拠

ORDレコード
ord-d8fd525791f841c58f2b2477bc4d190f
出典データセット
uspto-grants-2015_01
特許番号
US08940724B2

反応ノート

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