Lithium Hexamethyldisilazide → HCID 66611412、化合物

HRID 1621841ノート

反応式

HRID 1621841 の反応式
F[C:2]1[C:7]([C:8]2[N:13]=[C:12]([CH3:14])[N:11]=[C:10]([N:15]([CH2:25][C:26]3[CH:31]=[CH:30][C:29]([O:32][CH3:33])=[CH:28][CH:27]=3)[CH2:16][C:17]3[CH:22]=[CH:21][C:20]([O:23][CH3:24])=[CH:19][CH:18]=3)[N:9]=2)=[CH:6][C:5]([C@H:34]([N:36]2[CH2:41][CH2:40][N:39]([S:42]([CH3:45])(=[O:44])=[O:43])[CH2:38][CH2:37]2)[CH3:35])=[CH:4][N:3]=1.[F:46][C:47]1[CH:56]=[C:55]([NH2:57])[CH:54]=[C:53]2[C:48]=1[CH:49]=[CH:50][CH:51]=[N:52]2.C[Si]([N-][Si](C)(C)C)(C)C.[Li+]>C1COCC1.[NH4+].[Cl-]>[CH3:24][O:23][C:20]1[CH:19]=[CH:18][C:17]([CH2:16][N:15]([CH2:25][C:26]2[CH:31]=[CH:30][C:29]([O:32][CH3:33])=[CH:28][CH:27]=2)[C:10]2[N:11]=[C:12]([CH3:14])[N:13]=[C:8]([C:7]3[C:2]([NH:57][C:55]4[CH:54]=[C:53]5[C:48]([CH:49]=[CH:50][CH:51]=[N:52]5)=[C:47]([F:46])[CH:56]=4)=[N:3][CH:4]=[C:5]([C@H:34]([N:36]4[CH2:41][CH2:40][N:39]([S:42]([CH3:45])(=[O:43])=[O:44])[CH2:38][CH2:37]4)[CH3:35])[CH:6]=3)[N:9]=2)=[CH:22][CH:21]=1

参加物

6

反応物 3

HCID 2733832Lithium HexamethyldisilazideHCID 666002875-Fluoroquinolin-7-amineHCID 66611822(R)-4-(2-fluoro-5-(1-(4-(methylsulfonyl)piperazin-1-yl)ethyl)pyridin-3-yl)-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amine

生成物 1

HCID 66611412HCID 66611412、化合物収率 71.4%

試薬・触媒・溶媒 2

HCID 8028Tetrahydrofuran溶媒HCID 25517Ammonium Chloride溶媒

反応条件

温度
0 °C

実験手順

A mixture of (R)-4-(2-fluoro-5-(1-(4-(methylsulfonyl)piperazin-1-yl)ethyl)pyridin-3-yl)-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amine (Example 146, Step 6) (140 mg, 0.220 mmol), 5-fluoroquinolin-7-amine (35.7 mg, 0.220 mmol) and lithium bis(trimethylsilyl)amide (1.0 M in THF; 0.661 mL, 0.661 mmol, Aldrich) in THF (3 mL) was stirred at 0° C. for 1 h. The reaction mixture was diluted with saturated NH4Cl (10 mL) and extracted with EtOAc (2×30 mL). The organic extract was washed with saturated NaCl (10 mL) and dried over Na2SO4. The solution was filtered and concentrated in vacuo to give the crude material as yellow oil. The crude product was purified by silica gel chromatography eluting with EtOAc to give (R)—N-(3-(4-(bis(4-methoxybenzyl)amino)-6-methyl-1,3,5-triazin-2-yl)-5-(1-(4-(methylsulfonyl)piperazin-1-yl)ethyl)pyridin-2-yl)-5-fluoroquinolin-7-amine (122 mg, 0.157 mmol, 71.2% yield). 1H NMR (300 MHz, CDCl3) δ 1.40 (d, J=6.72 Hz, 3H) 2.57 (dd, J=11.91, 4.17 Hz, 4H) 2.65 (s, 3H) 2.67 (s, 3H) 3.07-3.24 (m, 4H) 3.81 (s, 3H) 4.76-4.98 (m, 4H) 6.86 (dd, J=12.28, 8.62 Hz, 4H) 7.11-7.25 (m, 9H) 7.38-7.52 (m, 1H) 7.82 (d, J=8.48 Hz, 1H) 8.42 (d, J=2.19 Hz, 1H) 8.77 (d, J=2.34 Hz, 1H) 8.91 (d, J=2.49 Hz, 1H) 9.14 (d, J=2.05 Hz, 1H) 12.57 (s, 1H). m/z (ESI, +ve ion) 778.1 (M+H)+.

後処理

  1. extractionextracted with EtOAc (2×30 mL)
  2. extractionThe organic extract
  3. washwas washed with saturated NaCl (10 mL)
  4. dry with materialdried over Na2SO4
  5. filtrationThe solution was filtered
  6. concentrationconcentrated in vacuo
  7. customto give the crude material as yellow oil
  8. customThe crude product was purified by silica gel chromatography
  9. washeluting with EtOAc

出典と根拠

ORDレコード
ord-ac168172296943f3b9b1e5c0d696ce39
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…