Tetrahydrofuran → N-(5-(3-(4-Amino-6-methyl-1,3,5-triazin-2-YL)pyridin-2-ylamino)-2-methylpyridin-3-YL)methanesulfonamide

HRID 1812431ノート

反応式

HRID 1812431 の反応式
F[C:2]1[C:7]([C:8]2[N:13]=[C:12]([CH3:14])[N:11]=[C:10]([NH2:15])[N:9]=2)=[CH:6][CH:5]=[CH:4][N:3]=1.[NH2:16][C:17]1[CH:18]=[C:19]([NH:24][S:25]([CH3:28])(=[O:27])=[O:26])[C:20]([CH3:23])=[N:21][CH:22]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Na+].C1COCC1>CN(C=O)C>[NH2:15][C:10]1[N:11]=[C:12]([CH3:14])[N:13]=[C:8]([C:7]2[C:2]([NH:16][C:17]3[CH:18]=[C:19]([NH:24][S:25]([CH3:28])(=[O:27])=[O:26])[C:20]([CH3:23])=[N:21][CH:22]=3)=[N:3][CH:4]=[CH:5][CH:6]=2)[N:9]=1

参加物

6

反応物 4

HCID 8028TetrahydrofuranHCID 2724254Sodium bis(trimethylsilyl)amideHCID 665998524-(2-Fluoropyridin-3-yl)-6-methyl-1,3,5-triazin-2-amineHCID 66600561N-(5-amino-2-methylpyridin-3-yl)methanesulfonamide

生成物 1

HCID 59548449N-(5-(3-(4-Amino-6-methyl-1,3,5-triazin-2-YL)pyridin-2-ylamino)-2-methylpyridin-3-YL)methanesulfonamide収率 41.4%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

反応条件

温度
0 °C

実験手順

To a 15 mL round-bottom flask was added 4-(2-fluoropyridin-3-yl)-6-methyl-1,3,5-triazin-2-amine (0.045 g, 0.219 mmol), N-(5-amino-2-methylpyridin-3-yl)methanesulfonamide (0.049 g, 0.241 mmol), and DMF (2.0 mL). The mixture was cooled to 0° C. under N2. Sodium bis(trimethylsilyl)amide, 1.0 m in THF (Aldrich) (0.178 mL, 0.877 mmol) was then added to the solution in one portion. The now burgundy color mixture was stirred at 0° C. for 10 min then warmed up to rt and stirred for 1 h. The reaction mixture was quenched with sat. NH4Cl and partitioned between water and CHCl3. The aqueous layer was extracted with more CHCl3 (2×10 mL). The combined organic layers were dried over MgSO4 and concentrated. The crude product was purified by column chromatography (16 g, 5% to 10% MeOH in DCM) to afford the desired product as a yellow solid (35 mg). MS (ESI pos. ion) m/z: 387.0. 1H NMR (300 MHz, DMSO-d6) δ ppm 2.46 (d, J=9.06 Hz, 6H) 3.06 (s, 3H) 3.33 (s, 3H) 6.96 (dd, J=7.60, 4.68 Hz, 1H) 7.75 (br. s., 1H) 7.87 (br. s., 1H) 8.27-8.41 (m, 2H) 8.67 (d, J=2.05 Hz, 1H) 8.79 (dd, J=7.82, 1.53 Hz, 1H) 9.30 (br. s., 1H) 12.03 (s, 1H).

後処理

  1. temperaturethen warmed up to rt
  2. stirringstirred for 1 h
  3. customThe reaction mixture was quenched with sat. NH4Cl
  4. custompartitioned between water and CHCl3
  5. extractionThe aqueous layer was extracted with more CHCl3 (2×10 mL)
  6. dry with materialThe combined organic layers were dried over MgSO4
  7. concentrationconcentrated
  8. customThe crude product was purified by column chromatography (16 g, 5% to 10% MeOH in DCM)

出典と根拠

ORDレコード
ord-2de7430a81a64825a0c987e37a5facab
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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