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 1431602노트

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HRID 1431602 반응식
[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

참가 물질

7

반응물 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

생성물 1

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

시약·촉매·용매 2

HCID 6102075Dichlorobis(triphenylphosphine)palladium촉매HCID 962Water용매

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온도
95 °C

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-d8fd525791f841c58f2b2477bc4d190f
출처 데이터셋
uspto-grants-2015_01
특허 번호
US08940724B2

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