Sodium Carbonate → (S)-2-(1-((2-aminopyrido[3,2-d]pyrimidin-4-yl)amino)ethyl)-5-(2-methylpyrimidin-5-yl)-3-phenylquinazolin-4(3H)-one

HRID 869467ノート

反応式

HRID 869467 の反応式
[NH2:1][C:2]1[N:3]=[C:4]([NH:12][C@H:13]([C:15]2[N:24]([C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)[C:23](=[O:31])[C:22]3[C:17](=[CH:18][CH:19]=[CH:20][C:21]=3Cl)[N:16]=2)[CH3:14])[C:5]2[N:11]=[CH:10][CH:9]=[CH:8][C:6]=2[N:7]=1.[CH3:33][C:34]1[N:39]=[CH:38][C:37](B2OC(C)(C)C(C)(C)O2)=[CH:36][N:35]=1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC(C)C)=CC=CC=2OC(C)C)CCCCC1.C([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1.O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[NH2:1][C:2]1[N:3]=[C:4]([NH:12][C@H:13]([C:15]2[N:24]([C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)[C:23](=[O:31])[C:22]3[C:17](=[CH:18][CH:19]=[CH:20][C:21]=3[C:37]3[CH:36]=[N:35][C:34]([CH3:33])=[N:39][CH:38]=3)[N:16]=2)[CH3:14])[C:5]2[N:11]=[CH:10][CH:9]=[CH:8][C:6]=2[N:7]=1

参加物

7

反応物 4

HCID 10340Sodium CarbonateHCID 162179852-Dicyclohexylphosphino-2',6'-diisopropoxybiphenylHCID 457872822-Methyl-5-(tetramethyl-1,3,2-dioxaborolan-2-yl)pyrimidineHCID 71232775(S)-2-(1-((2-aminopyrido[3,2-d]pyrimidin-4-yl)amino)ethyl)-5-chloro-3-phenylquinazolin-4(3H)-one

生成物 1

HCID 71226709(S)-2-(1-((2-aminopyrido[3,2-d]pyrimidin-4-yl)amino)ethyl)-5-(2-methylpyrimidin-5-yl)-3-phenylquinazolin-4(3H)-one収率 50.6%

試薬・触媒・溶媒 2

HCID 167845palladium(II) acetate触媒HCID 218864351,4-Dioxane--water (1/1)溶媒

反応条件

温度
120 °C

実験手順

To a solution of (S)-2-(1-((2-aminopyrido[3,2-d]pyrimidin-4-yl)amino)ethyl)-5-chloro-3-phenylquinazolin-4(3H)-one (30 mg, 0.067 mmol) and 2-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrimidine (22 mg, 0.1 mmol) in 1,4-dioxane-H2O (4:1, 2 mL) in a sealed tube, 2-dicyclohexylphosphino-2′,6′-diisopropoxybiphenyl (15.6 mg, 0.034 mmol), palladium(II) acetate (3.8 mg, 0.017 mmol), and Na2CO3 (21 mg, 0.20 mmol) were added sequentially. The mixture was degassed and backfilled with argon (three cycles), and then stirred at 120° C. for 1 h. The mixture was allowed to cool to RT, and then partitioned between ethyl acetate and water. The organic layer was washed with brine, dried over Na2SO4 and filtered. The filtrate was concentrated in vacuo and the residue was purified by ISCO column chromatography (silica gel cartridge, 0-10% MeOH/DCM) to afford compound I-91, (S)-2-(1-((2-aminopyrido[3,2-d]pyrimidin-4-yl)amino)ethyl)-5-(2-methylpyrimidin-5-yl)-3-phenylquinazolin-4(3H)-one (17 mg, 50% yield). ESI-MS m/z: 502.2 [M+H]+.

後処理

  1. customThe mixture was degassed
  2. temperatureto cool to RT
  3. custompartitioned between ethyl acetate and water
  4. washThe organic layer was washed with brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationThe filtrate was concentrated in vacuo
  8. customthe residue was purified by ISCO column chromatography (silica gel cartridge, 0-10% MeOH/DCM)

出典と根拠

ORDレコード
ord-314b257151eb418aa1e45b1ab754281d
出典データセット
uspto-grants-2015_03
特許番号
US08969363B2

反応ノート

読み込み中…