Potassium Carbonate → Tirbanibulin

HRID 547429

반응식

HRID 547429 반응식
[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

참가 물질

5

반응물 3

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

생성물 1

HCID 23635314Tirbanibulin수율 79%

시약·촉매·용매 1

HCID 702Ethanol용매

반응 조건

온도
150 °C

실험 절차

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 10071 (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]+. 1 Polymer bound di(acetato)dicyclohexylphenylphosphinepalladium(II), manufactured by Johnson Matthey, Inc. and available from Aldrich (catalog #590231).

후처리

  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

출처 및 근거

ORD 기록
ord-20b4cc934c5c470f9a829c01f1c9a8de
출처 데이터셋
uspto-grants-2011_05
특허 번호
US07939529B2

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