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

HRID 1811947ノート

反応式

HRID 1811947 の反応式
Cl[C:2]1[N:7]=[C:6]([NH:8][C:9]2[CH:10]=[N:11][C:12]([O:15][CH3:16])=[CH:13][CH:14]=2)[C:5]([C:17]2[N:22]=[C:21]([CH3:23])[N:20]=[C:19]([S:24][CH3:25])[N:18]=2)=[CH:4][N:3]=1.[F:26][C:27]1[CH:32]=[CH:31][C:30](B(O)O)=[CH:29][CH:28]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.O.[NH4+].[Cl-].[Pd+2].ClC1C=C[C-](P(C2C=CC=CC=2)C2C=CC=CC=2)C=1Cl.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2]>[F:26][C:27]1[CH:32]=[CH:31][C:30]([C:2]2[N:7]=[C:6]([NH:8][C:9]3[CH:10]=[N:11][C:12]([O:15][CH3:16])=[CH:13][CH:14]=3)[C:5]([C:17]3[N:22]=[C:21]([CH3:23])[N:20]=[C:19]([S:24][CH3:25])[N:18]=3)=[CH:4][N:3]=2)=[CH:29][CH:28]=1

参加物

8

反応物 3

HCID 10796Cesium carbonateHCID 2856454-Fluorophenylboronic acidHCID 866470542-chloro-N-(6-methoxypyridin-3-yl)-5-(4-methyl-6-(methylthio)-1,3,5-triazin-2-yl)pyrimidin-4-amine

生成物 1

HCID 665998562-(4-fluorophenyl)-N-(6-methoxypyridin-3-yl)-5-(4-methyl-6-(methylthio)-1,3,5-triazin-2-yl)pyrimidin-4-amine収率 52.5%

試薬・触媒・溶媒 4

HCID 178478230HCID 178478230、化合物触媒HCID 962Water溶媒HCID 25517Ammonium Chloride溶媒HCID 312751,4-Dioxane溶媒

反応条件

温度
100 °C

実験手順

A mixture of 2-chloro-N-(6-methoxypyridin-3-yl)-5-(4-methyl-6-(methylthio)-1,3,5-triazin-2-yl)pyrimidin-4-amine (38 mg, 0.101 mmol), 4-fluorobenzeneboronic acid (16.98 mg, 0.121 mmol), dichloro 1,1′-bis(diphenylphosphino)ferrocene palladium(II) (8.26 mg, 10.11 μmol) and cesium carbonate (66 mg, 0.202 mmol) in dioxane (3 mL) and water (0.5 mL) was stirred at 100° C. for 1 h. The mixture was cooled down to room temperature. The reaction mixture was diluted with saturated NH4Cl (5 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 material as an orange solid. The crude product was purified by silica gel chromatography eluting with 30% EtOAc/hexanes to give 2-(4-fluorophenyl)-N-(6-methoxypyridin-3-yl)-5-(4-methyl-6-(methylthio)-1,3,5-triazin-2-yl)pyrimidin-4-amine (23 mg, 0.053 mmol, 52.2% yield). 1H NMR (300 MHz, CDCl3) δ 11.64 (s, 1H); 9.73 (s, 1H); 8.39-8.50 (m, 3H); 8.11 (dd, J=8.77, 2.48 Hz, 1H); 7.16 (t, J=8.62 Hz, 2H); 6.87 (d, J=8.92 Hz, 1H); 4.00 (s, 3H); 2.67 (d, J=4.38 Hz, 6H). m/z (ESI, +ve ion) 436.1 (M+H)+.

後処理

  1. temperatureThe mixture was cooled down to room temperature
  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 material as an orange solid
  9. customThe crude product was purified by silica gel chromatography
  10. washeluting with 30% EtOAc/hexanes

出典と根拠

ORDレコード
ord-b91ea42176e14d85bab2476a3411a721
出典データセット
uspto-grants-2013_01
特許番号
US08362241B2

反応ノート

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