Potassium Carbonate → Tirbanibulin

HRID 545153

反応式

HRID 545153 の反応式
[CH2:1]([NH:8][C:9](=[O:18])[CH2:10][C:11]1[CH:16]=[CH:15][C:14](Br)=[CH:13][N:12]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CC1(C)C(C)(C)OB([C:27]2[CH:41]=[CH:40][C:30]([O:31][CH2:32][CH2:33][N:34]3[CH2:39][CH2:38][O:37][CH2:36][CH2:35]3)=[CH:29][CH:28]=2)O1.C(=O)([O-])[O-].[K+].[K+]>C(O)C>[CH:5]1[CH:4]=[CH:3][C:2]([CH2:1][NH:8][C:9]([CH2:10][C:11]2[CH:16]=[CH:15][C:14]([C:27]3[CH:28]=[CH:29][C:30]([O:31][CH2:32][CH2:33][N:34]4[CH2:35][CH2:36][O:37][CH2:38][CH2:39]4)=[CH:40][CH:41]=3)=[CH:13][N:12]=2)=[O:18])=[CH:7][CH:6]=1

参加物

5

反応物 3

HCID 11430Potassium CarbonateHCID 46259104-(2-Morpholin-4-ylethoxy)benzeneboronic acid, pinacol esterHCID 59000711N-benzyl-2-(5-bromopyridin-2-yl)acetamide

生成物 1

HCID 23635314Tirbanibulin収率 79%

試薬・触媒・溶媒 1

HCID 702Ethanol溶媒

反応条件

温度
150 °C

実験手順

A 10 mL reaction tube with a septum closure and stir bar was charged with N-benzyl-2-(5-bromopyridin-2-yl)acetamide (123 mg, 0.403 mmol), 4-(2-(4-(4,4,5,5-tetramethyl[1,3,2]dioxaborolan-2-yl)-phenoxy)ethyl)morpholine (171 mg, 0.513 mmol), and FibreCat 1007 (30 mg, 0.015 mmol). Ethanol (3 mL) was added, followed by aqueous potassium carbonate solution (0.60 mL, 1.0 M, 0.60 mmol). The tube was sealed and heated under microwave conditions at 150° C. for 10 minutes. The reaction was cooled and concentrated to remove the majority of the ethanol, and then taken up in 10 mL of ethyl acetate and washed successively with water and saturated sodium chloride solution. The organic layer was dried with MgSO4, filtered and concentrated to a white solid. This white solid was triturated with ethyl ether to give KX2-391 as a white solid (137 mg, 79%): mp 135-137° C.; 1H NMR (300 MHz, CDCl3) δ 8.70 (d, 1H, J=2.0 Hz), 7.81 (dd, 1H, J=2.4 Hz, J=8.0 Hz), 7.65 (br s, 1H), 7.49 (d, 2H, J=8.8 Hz), 7.37-7.20 (m, 6H), 7.01 (d, 2H, J=8.8 Hz), 4.49 (d, 2H, J=5.8 Hz), 4.16 (t, 2H, J=5.7 Hz, 3.82 (s, 2H), 3.78-3.72 (m, 4H), 2.84 (t, 2H, J=5.7 Hz), 2.62-2.58 (m, 4H); HPLC (Method B) 98.0% (AUC), tR=1.834 min.; APCI MS m/z 432 [M+H]+.

後処理

  1. customA 10 mL reaction tube with a septum closure
  2. customThe tube was sealed
  3. temperatureThe reaction was cooled
  4. concentrationconcentrated
  5. customto remove the majority of the ethanol
  6. washwashed successively with water and saturated sodium chloride solution
  7. dry with materialThe organic layer was dried with MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated to a white solid
  10. customThis white solid was triturated with ethyl ether

出典と根拠

ORDレコード
ord-2cc2685d3de24857b6c527138e49c106
出典データセット
uspto-grants-2011_05
特許番号
US07935697B2

関連ノート

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