Lithium Hexamethyldisilazide → N-(5-(3-(4-(Bis(4-methoxybenzyl)amino)-6-methyl-1,3,5-triazin-2-YL)pyridin-2-ylamino)-2-chloropyridin-3-YL)-4-fluorobenzenesulfonamide

HRID 1621787

反応式

HRID 1621787 の反応式
[NH2:1][C:2]1[CH:3]=[C:4]([NH:9][S:10]([C:13]2[CH:18]=[CH:17][C:16]([F:19])=[CH:15][CH:14]=2)(=[O:12])=[O:11])[C:5]([Cl:8])=[N:6][CH:7]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+].F[C:31]1[C:36]([C:37]2[N:42]=[C:41]([CH3:43])[N:40]=[C:39]([N:44]([CH2:54][C:55]3[CH:60]=[CH:59][C:58]([O:61][CH3:62])=[CH:57][CH:56]=3)[CH2:45][C:46]3[CH:51]=[CH:50][C:49]([O:52][CH3:53])=[CH:48][CH:47]=3)[N:38]=2)=[CH:35][CH:34]=[CH:33][N:32]=1>C1COCC1>[CH3:62][O:61][C:58]1[CH:57]=[CH:56][C:55]([CH2:54][N:44]([CH2:45][C:46]2[CH:47]=[CH:48][C:49]([O:52][CH3:53])=[CH:50][CH:51]=2)[C:39]2[N:40]=[C:41]([CH3:43])[N:42]=[C:37]([C:36]3[C:31]([NH:1][C:2]4[CH:3]=[C:4]([NH:9][S:10]([C:13]5[CH:14]=[CH:15][C:16]([F:19])=[CH:17][CH:18]=5)(=[O:11])=[O:12])[C:5]([Cl:8])=[N:6][CH:7]=4)=[N:32][CH:33]=[CH:34][CH:35]=3)[N:38]=2)=[CH:60][CH:59]=1

参加物

5

反応物 3

HCID 2733832Lithium HexamethyldisilazideHCID 595482404-(2-fluoropyridin-3-yl)-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amineHCID 71480919N-(5-amino-2-chloropyridin-3-yl)-4-fluorobenzenesulfonamide

生成物 1

HCID 86647062N-(5-(3-(4-(Bis(4-methoxybenzyl)amino)-6-methyl-1,3,5-triazin-2-YL)pyridin-2-ylamino)-2-chloropyridin-3-YL)-4-fluorobenzenesulfonamide収率 46.7%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒2 回

反応条件

温度
0 °C

実験手順

A mixture of N-(5-amino-2-chloropyridin-3-yl)-4-fluorobenzenesulfonamide (0.08 g, 0.265 mmol) in THF (5 mL) was cooled to 0° C. under N2. Lithium bis(trimethylsilyl)amide, 1.0 M solution in tetrahydrofuran (Aldrich) (0.795 mL, 0.795 mmol) was added dropwise and the mixture was stirred at 0° C. for 30 min before 4-(2-fluoropyridin-3-yl)-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amine (0.142 g, 0.318 mmol) was added. The resulting mixture was stirred at 0° C. for 10 min then removed from the ice bath and stirred for 3 h. The reaction mixture was quenched with water. The resulting mixture was partitioned between EtOAc and sat. NH4Cl. The aqueous layer was extracted with EtOAc (2×10 mL). The combined organic layers were washed with water, brine, dried over MgSO4 and concentrated. The crude product was purified by column chromatography (40 g, 20% to 30% acetone in hexanes) to give the product as a yellow solid (0.090 g). m/z (ESI, +ve ion) 727.1 (M+H)+. 1H NMR (300 MHz, CDCl3) δ 12.48 (s, 1H); 8.78-8.95 (m, 2H); 8.41 (d, J=3.51Hz, 1H); 8.27 (s, 1H); 7.93 (dd, J=8.62, 4.97 Hz, 2H); 7.22 (d, J=6.58 Hz, 4H); 7.14 (t, J=8.48 Hz, 2H); 6.77-6.97 (m, 6H); 4.85 (d, J=3.36 Hz, 4H); 3.81 (d, J=5.12 Hz, 6H); 2.61 (s, 3H).

後処理

  1. additionwas added
  2. customthen removed from the ice bath
  3. stirringstirred for 3 h
  4. customThe reaction mixture was quenched with water
  5. customThe resulting mixture was partitioned between EtOAc and sat. NH4Cl
  6. extractionThe aqueous layer was extracted with EtOAc (2×10 mL)
  7. washThe combined organic layers were washed with water, brine
  8. dry with materialdried over MgSO4
  9. concentrationconcentrated
  10. customThe crude product was purified by column chromatography (40 g, 20% to 30% acetone in hexanes)

出典と根拠

ORDレコード
ord-959805cba4f14d37bdf3eca8b33b9c9f
出典データセット
uspto-grants-2014_07
特許番号
US08772480B2

関連ノート

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