Chloroacetyl chloride → HCID 11598700, compound

HRID 422631Notes

Reaction equation

HRID 422631 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.[Cl:43][CH2:44][C:45](Cl)=[O:46]>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:45](=[O:46])[CH2:44][Cl:43])[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 6577Chloroacetyl chloride2×HCID 81531DiisopropylethylamineHCID 11517695HCID 11517695, compound

Product 1

HCID 11598700HCID 11598700, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

1-(2-phenylquinolin-7-yl)-3-(piperidin-4-ylmethyl)-imidazo-[1,5-a]-pyrazin-8-amine (110.00 mg, 0.25 mmol) in a dried 15 mL round bottom flask was dissolved in 2.00 mL of methylene chloride and was charged with PS-DIEA (150 mg, 0.46 mmol). Chloroacetyl chloride (10 μL, 0.42 equiv) was added in one portion. After 10 min., another 5 μL of chloroacetyl chloride (0.21 equiv) was added. After another 10 min., another 2.5 μL of methoxylacetyl (0.11 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 a 5 g Jones silica gel (dry loaded with silica, wetted with 100% ethyl acetate and eluted with 5% NH3 in MeOH/Ethyl Acetate) and afforded the desired product; 1H NMR (400 MHz, CHLOROFORM-d) δ 8.74 (1H, s), 8.30 (1H, d, J=8.68), 8.21 (2H, d, J=7.01), 7.98 (2H, m), 7.86 (1H, dd, J=1.70, J=1.70), 7.53 (3H, m), 7.24 (1H, d, J=5.34), 7.08 (1H, d, J=5.31), 4.63 (1H, d, J=13.24), 3.90 (1H, d, J=13.2), 3.15 (1H, t), 2.97 (2H, d, J=5.64), 2.70 (1H, t), 2.34 (1H, m), 2.05 (2H, s), 1.92 (2H, t), 1.42 (2H, m); MS (ES+): m/z 511.06/513.02 (50/25) [MH+]; HPLC: tR=2.20 min (OpenLynx, polar—5 min).

Workup

  1. waitAfter another 10 min.
  2. additionanother 2.5 μL of methoxylacetyl (0.11 equiv) was added
  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 a 5 g Jones silica gel (dry loaded with silica, wetted with 100% ethyl acetate and eluted with 5% NH3 in MeOH/Ethyl Acetate)

Sources & evidence

ORD record
ord-a5346c6a70ec4970b79e3dcb4aefd949
Source dataset
uspto-grants-2012_01
Patent number
US08101613B2

Reaction notes

Loading…