Methanesulfonyl chloride → Methanesulfonic acid 3-{4-[1-(4-isopropoxy-phenylcarbamoyl)-piperidin-4-yl]-quinazolin-6-yl}-prop-2-ynyl ester

HRID 657203ノート

反応式

HRID 657203 の反応式
[CH:1]([O:4][C:5]1[CH:10]=[CH:9][C:8]([NH:11][C:12]([N:14]2[CH2:19][CH2:18][CH:17]([C:20]3[C:29]4[C:24](=[CH:25][CH:26]=[C:27]([C:30]#[C:31][CH2:32][OH:33])[CH:28]=4)[N:23]=[CH:22][N:21]=3)[CH2:16][CH2:15]2)=[O:13])=[CH:7][CH:6]=1)([CH3:3])[CH3:2].CCN(C(C)C)C(C)C.[CH3:43][S:44](Cl)(=[O:46])=[O:45]>C(Cl)Cl>[CH:1]([O:4][C:5]1[CH:10]=[CH:9][C:8]([NH:11][C:12]([N:14]2[CH2:15][CH2:16][CH:17]([C:20]3[C:29]4[C:24](=[CH:25][CH:26]=[C:27]([C:30]#[C:31][CH2:32][O:33][S:44]([CH3:43])(=[O:46])=[O:45])[CH:28]=4)[N:23]=[CH:22][N:21]=3)[CH2:18][CH2:19]2)=[O:13])=[CH:7][CH:6]=1)([CH3:3])[CH3:2]

参加物

5

反応物 3

HCID 31297Methanesulfonyl chlorideHCID 81531DiisopropylethylamineHCID 587706514-[6-(3-Hydroxy-prop-1-ynyl)-quinazolin-4-yl]-piperidine-1-carboxylic acid (4-isopropoxy-phenyl)-amide

生成物 1

HCID 58770853Methanesulfonic acid 3-{4-[1-(4-isopropoxy-phenylcarbamoyl)-piperidin-4-yl]-quinazolin-6-yl}-prop-2-ynyl ester収率 93.2%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

反応条件

温度
0 °C

実験手順

A solution of 4-[6-(3-hydroxy-prop-1-ynyl)-quinazolin-4-yl]-piperidine-1-carboxylic acid (4-isopropoxy-phenyl)-amide (816 mg, 1.84 mmol), as prepared in Example 12, and DIEA (350 μL, 2.12 mmol) in DCM (13 mL) was treated with methanesulfonyl chloride (157 μL, 2.02 mmol) dropwise over 1 min with stirring at 0° C. under positive argon pressure. The ice bath was immediately removed, and the reaction was stirred at rt for 1 h 15 min. Flash chromatographic purification of the crude reaction mixture (1:9 hex/EtOAc→EtOAc) afforded the title compound (896 mg, 93%). 1H-NMR (300 MHz, CDCl3) δ 9.27 (s, 1H), 8.31 (d, 1H), 8.04 (d, 1H), 7.89 (dd, 1H), 7.26 (m, 2H), 6.85 (m, 2H), 6.34 (br s, 1H), 5.15 (s, 2H), 4.49 (heptet, 1H), 4.33-4.23 (m, 2H), 3.73 (m, 1H), 3.25-3.11 (m, 2H), 3.18 (s, 3H), 2.22-1.94 (m, 4H), 1.32 (d, 6H). LC/MS (ESI): calcd mass 522.2, found 523.3 (MH)+.

後処理

  1. customThe ice bath was immediately removed
  2. stirringthe reaction was stirred at rt for 1 h 15 min
  3. customFlash chromatographic purification of the crude
  4. customreaction mixture (1:9 hex/EtOAc→EtOAc)

出典と根拠

ORDレコード
ord-331ab806557b4db882d9541fff190a2f
出典データセット
uspto-grants-2011_12
特許番号
US08071768B2

反応ノート

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