Acetic Anhydride → HCID 178474853, compound

HRID 493776Notes

Reaction equation

HRID 493776 reaction equation
NC[CH:3]1[CH:6]([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)[CH2:5][CH2:4]1.[CH3:33][CH2:34][N:35]([CH:39](C)C)C(C)C.CC(OC(C)=O)=[O:44]>C(Cl)Cl>[NH2:16][C:15]1[C:10]2[N:11]([C:7]([C@@H:6]3[CH2:3][C@H:4]([CH2:39][NH:35][C:34](=[O:44])[CH3:33])[CH2:5]3)=[N:8][C:9]=2[C:17]2[CH:18]=[C:19]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:25][CH:26]=2)[CH:12]=[CH:13][N:14]=1

Participants

5

Reactant 3

HCID 7918Acetic AnhydrideHCID 81531DiisopropylethylamineHCID 68830493HCID 68830493, compound

Product 1

HCID 178474853HCID 178474853, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A suspension of 3-[4-(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).

Workup

  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

Sources & evidence

ORD record
ord-9669ee0ff4154ebab1dd018120f5a493
Source dataset
uspto-grants-2009_05
Patent number
US07534797B2

Reaction notes

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