Acetic Anhydride → HCID 178474853、化合物

HRID 386199ノート

反応式

HRID 386199 の反応式
[NH2:1][CH2:2][CH:3]1[CH2:6][CH:5]([C:7]2[N:11]3[CH:12]=[CH:13][N:14]=[C:15]([NH2:16])[C:10]3=[C:9]([C:17]3[CH:26]=[C:25]4[C:20]([CH:21]=[CH:22][C:23]([C:27]5[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=5)=[N:24]4)=[CH:19][CH:18]=3)[N:8]=2)[CH2:4]1.CCN(C(C)C)C(C)C.[CH3:42][C:43](OC(C)=O)=[O:44]>C(Cl)Cl>[NH2:16][C:15]1[C:10]2[N:11]([C:7]([C@@H:5]3[CH2:4][C@H:3]([CH2:2][NH:1][C:43](=[O:44])[CH3:42])[CH2:6]3)=[N:8][C:9]=2[C:17]2[CH:26]=[C:25]3[C:20]([CH:21]=[CH:22][C:23]([C:27]4[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=4)=[N:24]3)=[CH:19][CH:18]=2)[CH:12]=[CH:13][N:14]=1

参加物

5

反応物 3

HCID 7918Acetic AnhydrideHCID 81531DiisopropylethylamineHCID 11517376HCID 11517376、化合物

生成物 1

HCID 178474853HCID 178474853、化合物

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

A suspension of 3-[3-(aminomethyl)cyclobutyl]-1-(2-phenylquinolin-7-yl)imidazo[1,5-a]pyrazin-8-amine (0.237 mmol, 100 mg) in DCM (6 mL) was charged with DIEA (0.475 mmol, 83 μL) and Ac2O (0.237 mmol, 22.43 μL) at −40° C. The reaction solution was warmed to rt slowly and stirred under N2 for 1.5 h. The reaction was quenched with water (3 mL), diluted with methylene chloride (20 mL), washed with water (30 mL) and brine (30 mL), and dried (Na2SO4). The filtrate was concentrated under reduced pressure, and the crude material was purified by silica gel flush column chromatography (Jones Flashmaster, 10 g/70 mL cartridge), eluting with 3% MeOH (7 N NH3) in DCM, yielding the title compound as a light yellow solid. The sample was recrystallized from DCM (minimal amount) and EtOAc. The final product was obtained as an off-white solid; 1H NMR (400 MHz, CDCl3) δ 8.43-8.42 (m, 1H), 8.28 (dd, J=8.0 Hz, 0.4 Hz, 1H), 8.20-8.18 (m, 2H), 7.97-7.92 (m, 3H), 7.57-7.48 (m, 3H), 7.15 (d, J=4.8 Hz, 1H), 7.12 (d, J=5.2 Hz, 1H), 5.19 (b, 2H), 3.78-3.70 (m, 1H), 3.38 (t, J=5.6 Hz, 2H), 2.77-2.66 (m, 3H), 2.42-2.34 (m, 2H), 1.87 (s, 3H); MS (ES+): m/z 463 (100) [MH+]; HPLC: tR=2.06 min (OpenLynx, polar—5 min).

後処理

  1. customThe reaction was quenched with water (3 mL)
  2. additiondiluted with methylene chloride (20 mL)
  3. washwashed with water (30 mL) and brine (30 mL)
  4. dry with materialdried (Na2SO4)
  5. concentrationThe filtrate was concentrated under reduced pressure
  6. customthe crude material was purified by silica gel
  7. customflush column chromatography (Jones Flashmaster, 10 g/70 mL cartridge)
  8. washeluting with 3% MeOH (7 N NH3) in DCM

出典と根拠

ORDレコード
ord-aa24e9aa3ed340c2b03924d3988ea164
出典データセット
uspto-grants-2013_02
特許番号
US08367826B2

反応ノート

読み込み中…