Acetic Anhydride → HCID 178474853, 화합물

HRID 422636노트

반응식

HRID 422636 반응식
[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

참가 물질

5

반응물 3

HCID 7918Acetic AnhydrideHCID 81531DiisopropylethylamineHCID 11517376HCID 11517376, 화합물

생성물 1

HCID 178474853HCID 178474853, 화합물

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-a15d37feda6243aca4760d2f833e368c
출처 데이터셋
uspto-grants-2012_01
특허 번호
US08101613B2

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