Sodium Carbonate → 5,8-difluoro-N-(4-(3-(2-(methylamino)pyrimidin-4-yl)pyridin-2-yloxy)phenyl)-4-phenylphthalazin-1-amine

HRID 593957ノート

反応式

HRID 593957 の反応式
[C:1]1(B(O)O)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.Cl[C:11]1[C:20]2[C:15](=[C:16]([F:22])[CH:17]=[CH:18][C:19]=2[F:21])[C:14]([NH:23][C:24]2[CH:29]=[CH:28][C:27]([O:30][C:31]3[C:36]([C:37]4[CH:42]=[CH:41][N:40]=[C:39]([NH:43][CH3:44])[N:38]=4)=[CH:35][CH:34]=[CH:33][N:32]=3)=[CH:26][CH:25]=2)=[N:13][N:12]=1.O1CCOCC1.C(=O)([O-])[O-].[Na+].[Na+]>CCOC(C)=O.O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[F:21][C:19]1[CH:18]=[CH:17][C:16]([F:22])=[C:15]2[C:20]=1[C:11]([C:1]1[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1)=[N:12][N:13]=[C:14]2[NH:23][C:24]1[CH:25]=[CH:26][C:27]([O:30][C:31]2[C:36]([C:37]3[CH:42]=[CH:41][N:40]=[C:39]([NH:43][CH3:44])[N:38]=3)=[CH:35][CH:34]=[CH:33][N:32]=2)=[CH:28][CH:29]=1

参加物

8

反応物 4

HCID 10340Sodium CarbonateHCID 312751,4-DioxaneHCID 66827Phenylboronic AcidHCID 577562244-chloro-5,8-difluoro-N-(4-(3-(2-(methylamino)pyrimidin-4-yl)pyridin-2-yloxy)phenyl)phthalazin-1-amine

生成物 1

HCID 577562545,8-difluoro-N-(4-(3-(2-(methylamino)pyrimidin-4-yl)pyridin-2-yloxy)phenyl)-4-phenylphthalazin-1-amine

試薬・触媒・溶媒 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)触媒HCID 962Water溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
85 °C

実験手順

To phenylboronic acid (0.030 g, 0.24 mmol), 1,1′-bis(diphenylphosphino)ferrocene-palladium dichloride (0.0060 g, 0.0081 mmol) and 4-chloro-5,8-difluoro-N-(4-(3-(2-(methylamino)pyrimidin-4-yl)pyridin-2-yloxy)phenyl)phthalazin-1-amine (0.080 g, 0.16 mmol) was added dioxane (0.35 mL) and sodium carbonate (2.0 M, aqueous) (0.16 ml, 0.33 mmol). The resulting mixture was heated to 85° C. in a sealed tube for 60 minutes. The reaction was diluted with EtOAc and water, and the layers were separated and the organic layers were dried over sodium sulfate, filtered and concentrated. The crude was purified by ISCO silica gel chromatography (20-100% EtOAc/hexanes; 40 g column). Concentrated product fractions to yield 5,8-difluoro-N-(4-(3-(2-(methylamino)pyrimidin-4-yl)pyridin-2-yloxy)phenyl)-4-phenylphthalazin-1-amine as an off-white solid. MS m/z=534 [M+H]+. Calc'd for C30H21F2N7O: 533.54.

後処理

  1. customthe layers were separated
  2. dry with materialthe organic layers were dried over sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe crude was purified by ISCO silica gel chromatography (20-100% EtOAc/hexanes; 40 g column)

出典と根拠

ORDレコード
ord-b9dcafdc31b942c8b34d36f3fa512888
出典データセット
uspto-grants-2016_01
特許番号
US09242961B2

反応ノート

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