Dimethylformamide → N-methyl-6-(6-methyl-1-(3-(trifluoromethyl)phenoxy)isoquinolin-5-yl)quinazolin-2-amine

HRID 1668971ノート

反応式

HRID 1668971 の反応式
I[C:2]1[C:11]([CH3:12])=[CH:10][CH:9]=[C:8]2[C:3]=1[CH:4]=[CH:5][N:6]=[C:7]2[O:13][C:14]1[CH:19]=[CH:18][CH:17]=[C:16]([C:20]([F:23])([F:22])[F:21])[CH:15]=1.[CH3:24][NH:25][C:26]1[N:35]=[CH:34][C:33]2[C:28](=[CH:29][CH:30]=[C:31](B3OC(C)(C)C(C)(C)O3)[CH:32]=2)[N:27]=1.C(=O)([O-])[O-].[Na+].[Na+].CN(C=O)C>O.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[CH3:24][NH:25][C:26]1[N:35]=[CH:34][C:33]2[C:28](=[CH:29][CH:30]=[C:31]([C:2]3[C:11]([CH3:12])=[CH:10][CH:9]=[C:8]4[C:3]=3[CH:4]=[CH:5][N:6]=[C:7]4[O:13][C:14]3[CH:19]=[CH:18][CH:17]=[C:16]([C:20]([F:23])([F:22])[F:21])[CH:15]=3)[CH:32]=2)[N:27]=1

参加物

7

反応物 4

HCID 6228DimethylformamideHCID 10340Sodium CarbonateHCID 16086139N-Methyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-YL)quinazolin-2-amineHCID 58466470HCID 58466470、化合物

生成物 1

HCID 67339102N-methyl-6-(6-methyl-1-(3-(trifluoromethyl)phenoxy)isoquinolin-5-yl)quinazolin-2-amine

試薬・触媒・溶媒 2

HCID 178418476HCID 178418476、化合物触媒HCID 962Water溶媒2 回

反応条件

温度
150 °C

実験手順

5-Iodo-6-methyl-1-(3-(trifluoromethyl)phenoxy)isoquinoline (0.170 g, 0.396 mmol), N-methyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)quinazolin-2-amine (0.124 g, 0.436 mmol), dichlorobis(triphenyl-phosphine)palladium (II) (0.0139 g, 0.0198 mmol), and sodium carbonate (0.0840 g, 0.792 mmol) were all placed in a clear microwave vial along with 5 ml of 9:1 DMF:water. The vial was capped and heated in a Personal Chemistry SmithSynthesizer to 150° C. for 10 minutes. The reaction was diluted with water and extracted with EtAOc. The organic layer was washed (2×) with an aqueous saturated solution of sodium bicarbonate, then with water and then brine. The organic layer was then dried with sodium sulfate and purified by column chromatography on silica gel using a gradient of 30-70% EtOAc in hexanes. The clean fractions were reduced in vacuo and the residue triturated with ether to give N-methyl-6-(6-methyl-1-(3-(trifluoromethyl)phenoxy)isoquinolin-5-yl)quinazolin-2-amine as a light yellow solid. MS (M+H)+ 461.

後処理

  1. customThe vial was capped
  2. extractionextracted with EtAOc
  3. washThe organic layer was washed (2×) with an aqueous saturated solution of sodium bicarbonate
  4. dry with materialThe organic layer was then dried with sodium sulfate
  5. custompurified by column chromatography on silica gel using a gradient of 30-70% EtOAc in hexanes
  6. customthe residue triturated with ether

出典と根拠

ORDレコード
ord-ecc8d1686de842eb90bb461bbbab6ef2
出典データセット
uspto-grants-2011_08
特許番号
US07989461B2

反応ノート

読み込み中…