Acetic Anhydride → HCID 11719868, compound

HRID 1163141Notes

Reaction equation

HRID 1163141 reaction equation
[C:1]1([C:7]2[CH:16]=[CH:15][C:14]3[C:9](=[CH:10][C:11]([C:17]4[N:18]=[C:19]([CH2:27][CH:28]5[CH2:33][CH2:32][NH:31][CH2:30][CH2:29]5)[N:20]5[CH:25]=[CH:24][N:23]=[C:22]([NH2:26])[C:21]=45)=[CH:12][CH:13]=3)[N:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.CCN(C(C)C)C(C)C.[C:43](OC(=O)C)(=[O:45])[CH3:44]>C(Cl)Cl>[NH2:26][C:22]1[C:21]2[N:20]([C:19]([CH2:27][CH:28]3[CH2:33][CH2:32][N:31]([C:43](=[O:45])[CH3:44])[CH2:30][CH2:29]3)=[N:18][C:17]=2[C:11]2[CH:10]=[C:9]3[C:14]([CH:15]=[CH:16][C:7]([C:1]4[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=4)=[N:8]3)=[CH:13][CH:12]=2)[CH:25]=[CH:24][N:23]=1

Participants

5

Reactant 3

HCID 7918Acetic Anhydride4×HCID 81531DiisopropylethylamineHCID 11517695HCID 11517695, compound

Product 1

HCID 11719868HCID 11719868, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

1-(2-Phenyl-quinolin-7-yl)-3-piperidin-4-ylmethyl-imidazo[1,5-a]pyrazin-8-ylamine (100.00 mg, 0.23 mmol) in a dried 10 mL round-bottom flask was dissolved in 1.7 mL of methylene chloride and was charged with PS-DIEA (117.95 mg, 0.46 mmol). Acetic anhydride (Ac2O) (11 μL, 0.51 equiv) was added in one portion. After 15 min., another 5.5 μL of Ac2O (0.25 equiv) was added. After another 15 min., another 2.64 μL of Ac2O (0.12 equiv) was added. After another 15 min., another 11 μL of Ac2O (0.51 equiv) was added. The reaction was filtered through a fritted funnel, and the resins were rinsed multiple times with methylene chloride. The crude product was purified by silica gel flash chromatography (wetted with 100% EtOAc, eluted with 5% (7N NH3) in MeOH/EtOAc) and afforded the desired product; 1H NMR (400 MHz, CHLOROFORM-d) δ 8.41 (1H, d, J=1.68), 8.28 (1H, d, J=8.20), 8.19 (2H, dd, J=1.51 Hz, J=1.18), 7.93 (3H, m), 7.53 (3H, m), 7.23 (1H, d, J=5.10), 7.12 (1H, d, J=5.76), 5.55 (2H, m), 4.67 (1H, d, J=13.28), 3.83 (1H, d, J=12.26), 3.06 (1H, m), 2.96 (2H, m), 2.56 (1H, m), 2.27 (1H, m), 2.10 (3H, s), 1.85 (2H, t), 1.31 (2H, m); MS (ES+): m/z 477.11/478.08 (40/20) [MH+]; HPLC: tR=2.11 min (OpenLynx, polar—5 min).

Workup

  1. waitAfter another 15 min.
  2. waitAfter another 15 min.
  3. filtrationThe reaction was filtered through a fritted funnel
  4. washthe resins were rinsed multiple times with methylene chloride
  5. customThe crude product was purified by silica gel flash chromatography (wetted with 100% EtOAc, eluted with 5% (7N NH3) in MeOH/EtOAc)

Sources & evidence

ORD record
ord-7f6f49f87613463f9a525a732fbf0f0c
Source dataset
uspto-grants-2010_10
Patent number
US07820662B2

Reaction notes

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