4-Chloro-6-methyl-1,3,5-triazin-2-amine → 4-(5-(1-(Tert-butyldimethylsilyloxy)-2-methylpropan-2-yl)-2-fluoropyridin-3-yl)-6-methyl-1,3,5-triazin-2-amine

HRID 1812308

反応式

HRID 1812308 の反応式
[Si:1]([O:8][CH2:9][C:10]([C:13]1[CH:14]=[C:15](B(O)O)[C:16]([F:19])=[N:17][CH:18]=1)([CH3:12])[CH3:11])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].Cl[C:24]1[N:29]=[C:28]([CH3:30])[N:27]=[C:26]([NH2:31])[N:25]=1.C([O-])(=O)C.[K+]>O1CCOCC1.O.CC(P(C(C)(C)C)C1C=CC(N(C)C)=CC=1)(C)C.CC(P(C(C)(C)C)C1C=CC(N(C)C)=CC=1)(C)C.Cl[Pd]Cl>[Si:1]([O:8][CH2:9][C:10]([C:13]1[CH:14]=[C:15]([C:24]2[N:29]=[C:28]([CH3:30])[N:27]=[C:26]([NH2:31])[N:25]=2)[C:16]([F:19])=[N:17][CH:18]=1)([CH3:12])[CH3:11])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2]

参加物

7

反応物 3

HCID 305914-Chloro-6-methyl-1,3,5-triazin-2-amineHCID 517044Potassium AcetateHCID 665999945-(1-(Tert-butyldimethylsilyloxy)-2-methylpropan-2-yl)-2-fluoropyridin-3-ylboronic acid

生成物 1

HCID 666114554-(5-(1-(Tert-butyldimethylsilyloxy)-2-methylpropan-2-yl)-2-fluoropyridin-3-yl)-6-methyl-1,3,5-triazin-2-amine収率 34.5%

試薬・触媒・溶媒 3

HCID 11714597Bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II)触媒HCID 962Water溶媒HCID 312751,4-Dioxane溶媒

反応条件

温度
100 °C

実験手順

A yellow solution of 5-(1-(tert-butyldimethylsilyloxy)-2-methylpropan-2-yl)-2-fluoropyridin-3-ylboronic acid (177 mg, 0.541 mmol), 4-chloro-6-methyl-1,3,5-triazin-2-amine (Example 9; 78 mg, 0.541 mmol), bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II) (Aldrich, St. Louis, Mo.; 19.15 mg, 0.027 mmol), and potassium acetate (159 mg, 1.622 mmol) in a mixture of dioxane (4.0 mL) and water (1.0 mL) was stirred under argon at 100° C. for 2 h. The yellow reaction mixture was subsequently partitioned between CH2Cl2 (80 mL) and water (50 mL). The organic layer was separated, and the aqueous layer was extracted with CH2Cl2 (2×30 mL). The combined organic extracts were then dried over sodium sulfate and concentrated onto silica gel. Chromatographic purification (silica gel, 0 to 60% EtOAc/hexanes) provided 4-(5-(1-(tert-butyldimethylsilyloxy)-2-methylpropan-2-yl)-2-fluoropyridin-3-yl)-6-methyl-1,3,5-triazin-2-amine (73.0 mg, 0.186 mmol, 34.5% yield) as a white solid. 1H NMR (400 MHz, CDCl3) δ 8.56 (dd, J=9.2, 2.5 Hz, 1H), 8.33 (d, J=1.4 Hz, 1H), 5.65 (br. s., 2H), 3.57 (s, 2H), 2.54 (s, 3H), 1.37 (s, 6H), 0.84 (s, 9H), −0.03 (s, 6H). 19F NMR (377 MHz, CDCl3) δ −70.17 (d, J=9.2 Hz, 1 F). m/z (ESI, +ve) 392.3 (M+H)+.

後処理

  1. customThe yellow reaction mixture was subsequently partitioned between CH2Cl2 (80 mL) and water (50 mL)
  2. customThe organic layer was separated
  3. extractionthe aqueous layer was extracted with CH2Cl2 (2×30 mL)
  4. dry with materialThe combined organic extracts were then dried over sodium sulfate
  5. concentrationconcentrated onto silica gel
  6. customChromatographic purification (silica gel, 0 to 60% EtOAc/hexanes)

出典と根拠

ORDレコード
ord-0e8a5956bbf1436c94d66708d419437d
出典データセット
uspto-grants-2013_01
特許番号
US08362241B2

関連ノート

読み込み中…