Tetrahydrofuran → N-(6-methoxypyridin-3-yl)-5-(4-methyl-6-(methylthio)-1,3,5-triazin-2-yl)pyrimidin-4-amine

HRID 1621513ノート

反応式

HRID 1621513 の反応式
Br[C:2]1[C:3]([NH:8][C:9]2[CH:10]=[N:11][C:12]([O:15][CH3:16])=[CH:13][CH:14]=2)=[N:4][CH:5]=[N:6][CH:7]=1.[CH3:17][C:18]1[N:23]=[C:22]([S:24][CH3:25])[N:21]=[C:20]([Sn](CCCC)(CCCC)CCCC)[N:19]=1.[F-].[Cs+].C1COCC1>O.[Cu]I.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:16][O:15][C:12]1[N:11]=[CH:10][C:9]([NH:8][C:3]2[C:2]([C:20]3[N:19]=[C:18]([CH3:17])[N:23]=[C:22]([S:24][CH3:25])[N:21]=3)=[CH:7][N:6]=[CH:5][N:4]=2)=[CH:14][CH:13]=1

参加物

8

反応物 4

HCID 8028TetrahydrofuranHCID 25953Cesium fluorideHCID 601547172-Methyl-4-(methylthio)-6-(tributylstannyl)-1,3,5-triazineHCID 601557905-bromo-N-(6-methoxypyridin-3-yl)pyrimidin-4-amine

生成物 1

HCID 60155791N-(6-methoxypyridin-3-yl)-5-(4-methyl-6-(methylthio)-1,3,5-triazin-2-yl)pyrimidin-4-amine収率 53.7%

試薬・触媒・溶媒 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)触媒HCID 178418397HCID 178418397、化合物触媒HCID 962Water溶媒

反応条件

温度
140 °C

実験手順

A glass microwave reaction vessel was charged with 5-bromo-N-(6-methoxypyridin-3-yl)pyrimidin-4-amine (23 mg, 0.082 mmol), 2-methyl-4-(methylthio)-6-(tributylstannyl)-1,3,5-triazine (35.2 mg, 0.082 mmol), copper(I) iodide (15 mg, 0.082 mmol), cesium fluoride (206 mg, 0.82 mmol) and tetrakis(triphenylphosphine)palladium(0) (9.45 mg, 8.18 μmol) and THF (1 mL). The reaction mixture was stirred and heated in a Emrys Optimizer microwave reactor (Personal Chemistry, Biotage AB, Inc., Upssala, Sweden) at 140° C. for 30 min. The reaction mixture was diluted with water (10 mL) and extracted with EtOAc (2×30 mL). The organic extract was washed with saturated NaCl (5 mL) and dried over Na2SO4. The solution was filtered and concentrated in vacuo to give the crude product as a light-yellow solid. The crude product was purified by silica gel chromatography eluting with 60% EtOAc/hexanes to give N-(6-methoxypyridin-3-yl)-5-(4-methyl-6-(methylthio)-1,3,5-triazin-2-yl)pyrimidin-4-amine (15 mg, 0.044 mmol, 53.7% yield). 1H NMR (300 MHz, CDCl3) δ 11.58 (s, 1H); 9.65 (s, 1H); 8.74 (s, 1H); 8.35 (d, J=2.19 Hz, 1H); 8.07 (dd, J=8.84, 2.56 Hz, 1H); 6.82 (d, J=8.92 Hz, 1H); 3.96 (s, 3H); 2.67 (s, 3H); 2.65 (s, 3H). m/z (ESI, +ve ion) 342.0 (M+H)+.

後処理

  1. customA glass microwave reaction vessel
  2. extractionextracted with EtOAc (2×30 mL)
  3. extractionThe organic extract
  4. washwas washed with saturated NaCl (5 mL)
  5. dry with materialdried over Na2SO4
  6. filtrationThe solution was filtered
  7. concentrationconcentrated in vacuo
  8. customto give the crude product as a light-yellow solid
  9. customThe crude product was purified by silica gel chromatography
  10. washeluting with 60% EtOAc/hexanes

出典と根拠

ORDレコード
ord-1669fa78d9b7481ba1b868b09068782e
出典データセット
uspto-grants-2014_07
特許番号
US08772480B2

反応ノート

読み込み中…