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Bis-(1H-imidazol-2-YL)-methanone → (+/-)-Methyl 2-(4-(8-fluoro-1,2-dihydro-2-oxoquinazolin-3(4H)-yl)piperidine-1-carboxamido)-3-(7-methyl-1H-indazol-5-yl)propanoate

HRID 2099799
ノート
印刷プレビュー

反応式

HRID 2099799 の反応式
[CH3:1][O:2][C:3](=[O:17])[CH:4]([NH2:16])[CH2:5][C:6]1[CH:7]=[C:8]2[C:12](=[C:13]([CH3:15])[CH:14]=1)[NH:11][N:10]=[CH:9]2.[C:18](C1NC=CN=1)(C1NC=CN=1)=[O:19].[F:30][C:31]1[CH:32]=[CH:33][CH:34]=[C:35]2[C:40]=1[NH:39][C:38](=[O:41])[N:37]([CH:42]1[CH2:47][CH2:46][NH:45][CH2:44][CH2:43]1)[CH2:36]2>O1CCCC1>[F:30][C:31]1[CH:32]=[CH:33][CH:34]=[C:35]2[C:40]=1[NH:39][C:38](=[O:41])[N:37]([CH:42]1[CH2:47][CH2:46][N:45]([C:18]([NH:16][CH:4]([CH2:5][C:6]3[CH:7]=[C:8]4[C:12](=[C:13]([CH3:15])[CH:14]=3)[NH:11][N:10]=[CH:9]4)[C:3]([O:2][CH3:1])=[O:17])=[O:19])[CH2:44][CH2:43]1)[CH2:36]2
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

5

反応物 3

HCID 5250894Bis-(1H-imidazol-2-YL)-methanoneHCID 211022172(1h)-Quinazolinone,8-fluoro-3,4-dihydro-3-(4-piperidinyl)-HCID 58864334methyl 2-amino-3-(7-methyl-1H-indazol-5-yl)propanoate

生成物 1

HCID 11454987(+/-)-Methyl 2-(4-(8-fluoro-1,2-dihydro-2-oxoquinazolin-3(4H)-yl)piperidine-1-carboxamido)-3-(7-methyl-1H-indazol-5-yl)propanoate

試薬・触媒・溶媒 1

HCID 8028
Tetrahydrofuran
溶媒

反応条件

温度
0 °C

実験手順

A stirred solution of 2-amino-3-(7-methyl-1H-indazol-5-yl)-propionic acid methyl ester (0.36 g, 1.54 mmol) in tetrahydrofuran (15 mL) at 0° C. was treated with carbonyl diimidazole (0.20, 1.1 equiv). The reaction was stirred for min at 0° C., warmed to room temperature, stirred 10 min, and treated with 8-fluoro-3,4-dihydro-3-(piperidin-4-yl)quinazolin-2(1H)-one (0.38 g, 1.1 equiv). The mixture was stirred at room temperature overnight. The solvent was evaporated and the residue purified by column chromatography to give 0.41 g (53%) as a white powder. 1H-NMR (CDCl3, 500 MHz) δ 1.53-1.68 (m, 4H), 2.48 (s, 3H), 2.82 (m, 2H), 3.05 (m, 6H), 3.09 (dd, JAB=13.7, 6.1, 1H), 3.14 (dd, JAB=140.0, 6.1, 1H), 3.35 (bs, 1H), 3.68 (s, 3H), 3.88-4.02 (m, 2H), 4.22 (d, JAB=15.6, 1H), 4.25 (d, JAB=15.3, 1H), 4.44 (m, 1H), 4.71 (dd, J=6.1, 6.1, 1H), 6.78 (d, J=7.3, 1H), 6.84 (ddd, J=7.6, 7.6, 4.9, 1H), 6.88-6.95 (m, 2H), 7.28 (s, 1H), 7.91 (s, 1H). Mass spec.: 509.25 (MH)+.

後処理

  1. temperaturewarmed to room temperature
  2. stirringstirred 10 min
  3. stirringThe mixture was stirred at room temperature overnight
  4. customThe solvent was evaporated
  5. customthe residue purified by column chromatography
  6. customto give 0.41 g (53%) as a white powder

出典と根拠

ORDレコード
ord-25721cb4d8a84748bad1607d0971073c
出典データセット
uspto-grants-2009_08
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US07569578B2

反応ノート

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