Triethylamine → 1-(3-(tert-butyl)-1-(p-tolyl)-1H-pyrazol-5-yl)-3-(4-((2-((6-ethylpyrazin-2-yl)amino)pyridin-4-yl)methoxy)naphthalen-1-yl)urea

HRID 63362

反応式

HRID 63362 の反応式
C(N(CC)CC)C.[C:8]([C:12]1[CH:16]=[C:15]([NH:17][C:18](=[O:26])OC2C=CC=CC=2)[N:14]([C:27]2[CH:32]=[CH:31][C:30]([CH3:33])=[CH:29][CH:28]=2)[N:13]=1)([CH3:11])([CH3:10])[CH3:9].[CH2:34]([C:36]1[N:41]=[C:40]([NH:42][C:43]2[CH:48]=[C:47]([CH2:49][O:50][C:51]3[C:60]4[C:55](=[CH:56][CH:57]=[CH:58][CH:59]=4)[C:54]([NH:61]C(=O)OC(C)(C)C)=[CH:53][CH:52]=3)[CH:46]=[CH:45][N:44]=2)[CH:39]=[N:38][CH:37]=1)[CH3:35]>C1COCC1>[C:8]([C:12]1[CH:16]=[C:15]([NH:17][C:18]([NH:61][C:54]2[C:55]3[C:60](=[CH:59][CH:58]=[CH:57][CH:56]=3)[C:51]([O:50][CH2:49][C:47]3[CH:46]=[CH:45][N:44]=[C:43]([NH:42][C:40]4[CH:39]=[N:38][CH:37]=[C:36]([CH2:34][CH3:35])[N:41]=4)[CH:48]=3)=[CH:52][CH:53]=2)=[O:26])[N:14]([C:27]2[CH:28]=[CH:29][C:30]([CH3:33])=[CH:31][CH:32]=2)[N:13]=1)([CH3:10])([CH3:11])[CH3:9]

参加物

5

反応物 3

HCID 8471TriethylamineHCID 11057211phenyl (3-(tert-butyl)-1-(p-tolyl)-1H-pyrazol-5-yl)carbamate2 回HCID 118317293Tert-butyl (4-((2-((6-ethylpyrazin-2-yl)amino)pyridin-4-yl)methoxy)naphthalen-1-yl)carbamate2 回

生成物 1

HCID 918276051-(3-(tert-butyl)-1-(p-tolyl)-1H-pyrazol-5-yl)-3-(4-((2-((6-ethylpyrazin-2-yl)amino)pyridin-4-yl)methoxy)naphthalen-1-yl)urea

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

反応条件

温度
40 °C

実験手順

Triethylamine (0.013 mL, 0.093 mmol) was added to a solution of phenyl (3-(tert-butyl)-1-(p-tolyl)-1H-pyrazol-5-yl)carbamate (Intermediate B) (0.042 g, 0.121 mmol) and N-(4-(((4-aminonaphthalen-1-yl)oxy)methyl)pyridin-2-yl)-6-ethylpyrazin-2-amine (Intermediate D) (0.093 g, 0.250 mmol) in THF (1.5 mL) at 40° C. The reaction mixture was stirred at 40° C. for 40 min then cooled to RT and stirred for 3 days, and then concentrated in vacuo. The crude product was purified by silica gel chromatography (12 g column, 0 to 5% MeOH in DCM) to give an off white-brown solid. The product was re-purified by preparative HPLC (Gilson, Acidic (0.1% Formic acid), Acidic, Waters X-Select Prep-C18, 5 μm, 19×50 mm column, 45-75% MeCN in Water) to afford the title compound 1-(3-(tert-butyl)-1-(p-tolyl)-1H-pyrazol-5-yl)-3-(4-((2-((6-ethylpyrazin-2-yl)amino)pyridin-4-yl)methoxy)naphthalen-1-yl)urea as an off white solid (0.029 g, 49%); Rt 2.26 min (Method 1); m/z 627 (M+H)+ (ES+), 625 (M−H)− (ES−); 1H NMR δ: 1.18 (3H, t), 1.28 (9H, s), 2.40 (3H, s), 2.63 (2H, q), 5.36 (2H, s), 6.36 (1H, s), 7.02 (1H, d), 7.07 (1H, dd), 7.37 (2H, m), 7.45 (2H, m), 7.56-7.67 (3H, overlapping m), 7.94 (1H, m), 7.99 (1H, s), 8.02 (1H, s), 8.30 (1H, d), 8.39 (1H, m), 8.60 (1H, s), 8.81 (1H, s), 8.92 (1H, s), 10.08 (1H, s).

後処理

  1. temperaturethen cooled to RT
  2. stirringstirred for 3 days
  3. concentrationconcentrated in vacuo
  4. customThe crude product was purified by silica gel chromatography (12 g column, 0 to 5% MeOH in DCM)
  5. customto give an off white-brown solid
  6. customThe product was re-purified by preparative HPLC (Gilson, Acidic (0.1% Formic acid), Acidic, Waters X-Select Prep-C18, 5 μm, 19×50 mm column, 45-75% MeCN in Water)

出典と根拠

ORDレコード
ord-2d75221ba22f48c5a3ae8b4d16571249
出典データセット
uspto-grants-2016_09
特許番号
US09447076B2

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