Tetrahydrofuran → 7-methyl-N8-(3-(6-(methylamino)pyrimidin-4-yl)pyridin-2-yl)-N4-(3-(trifluoromethyl)phenyl)quinazoline-4,8-diamine

HRID 2092310ノート

反応式

HRID 2092310 の反応式
[CH3:1][C:2]1[C:11]([NH2:12])=[C:10]2[C:5]([C:6]([NH:13][C:14]3[CH:19]=[CH:18][CH:17]=[C:16]([C:20]([F:23])([F:22])[F:21])[CH:15]=3)=[N:7][CH:8]=[N:9]2)=[CH:4][CH:3]=1.Cl[C:25]1[C:30]([C:31]2[N:36]=[CH:35][N:34]=[C:33]([NH:37][CH3:38])[CH:32]=2)=[CH:29][CH:28]=[CH:27][N:26]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+].C1COCC1>O.C(OCC)(=O)C.O1CCOCC1>[CH3:1][C:2]1[C:11]([NH:12][C:25]2[C:30]([C:31]3[CH:32]=[C:33]([NH:37][CH3:38])[N:34]=[CH:35][N:36]=3)=[CH:29][CH:28]=[CH:27][N:26]=2)=[C:10]2[C:5]([C:6]([NH:13][C:14]3[CH:19]=[CH:18][CH:17]=[C:16]([C:20]([F:23])([F:21])[F:22])[CH:15]=3)=[N:7][CH:8]=[N:9]2)=[CH:4][CH:3]=1

参加物

8

反応物 4

HCID 8028TetrahydrofuranHCID 2733832Lithium HexamethyldisilazideHCID 589422526-(2-chloropyridin-3-yl)-N-methylpyrimidin-4-amineHCID 673386327-methyl-N4-(3-(trifluoromethyl)phenyl)quinazoline-4,8-diamine

生成物 1

HCID 673392747-methyl-N8-(3-(6-(methylamino)pyrimidin-4-yl)pyridin-2-yl)-N4-(3-(trifluoromethyl)phenyl)quinazoline-4,8-diamine

試薬・触媒・溶媒 3

HCID 962Water溶媒HCID 8857Ethyl Acetate溶媒HCID 312751,4-Dioxane溶媒

反応条件

温度
150 °C

実験手順

A mixture of 7-methyl-N4-(3-(trifluoromethyl)phenyl)quinazoline-4,8-diamine (0.083 g, 0.26 mmol) and 6-(2-chloropyridin-3-yl)-N-methylpyrimidin-4-amine (0.058 g, 0.26 mmol) were placed in a clear microwave vial along with 3 ml of dioxane. While stirring, lithium bis(trimethylsilyl)amide in THF (1.6 ml, 1.6 mmol) was added dropwise with a syringe to the reaction. The vial was capped and heated in a Personal Chemistry Smith Synthesizer to 150° C. for 12 minutes. The reaction was diluted with water and ethyl acetate. The organic portion was washed (2×) with an aqueous saturated solution of sodium bicarbonate, then with water and then brine. The residue was purified by HPLC using a gradient of 5% ACN 0.1% TFA to 95% ACN 0.1% TFA in water 0.1% TFA. The pure fractions were neutralized with ammonium hydroxide and the volatiles were removed under reduced pressure. The solid that crashed out of the aqueous layer was filtered off, washed with with water and dried in a vacuum oven at 45 degrees to give 7-methyl-N8-(3-(6-(methylamino)pyrimidin-4-yl)pyridin-2-yl)-N4-(3-(trifluoromethyl)phenyl)quinazoline-4,8-diamine as a light yellow solid. MS (M+H)+ 474.

後処理

  1. customThe vial was capped
  2. washThe organic portion was washed (2×) with an aqueous saturated solution of sodium bicarbonate
  3. customThe residue was purified by HPLC
  4. customthe volatiles were removed under reduced pressure
  5. filtrationwas filtered off
  6. washwashed with with water
  7. customdried in a vacuum oven at 45 degrees

出典と根拠

ORDレコード
ord-48b6cd62d9414cff9af3e9419d9a98d9
出典データセット
uspto-grants-2013_05
特許番号
US08440674B2

反応ノート

読み込み中…