1,2-Dichloroethane → 8-Chloro-1-iodo-3-[3-(4-methylpiperazin-1-yl)cyclobutyl]imidazo[1,5-a]pyrazine

HRID 550107Notes

Reaction equation

HRID 550107 reaction equation
[CH3:1][N:2]1[CH2:7][CH2:6][NH:5][CH2:4][CH2:3]1.ClCCCl.[Cl:12][C:13]1[C:14]2[N:15]([C:19]([CH:23]3[CH2:26][C:25](=O)[CH2:24]3)=[N:20][C:21]=2[I:22])[CH:16]=[CH:17][N:18]=1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>>[Cl:12][C:13]1[C:14]2[N:15]([C:19]([CH:23]3[CH2:26][CH:25]([N:5]4[CH2:6][CH2:7][N:2]([CH3:1])[CH2:3][CH2:4]4)[CH2:24]3)=[N:20][C:21]=2[I:22])[CH:16]=[CH:17][N:18]=1

Participants

5

Reactant 4

HCID 111,2-DichloroethaneHCID 531671-MethylpiperazineHCID 5049666Sodium triacetoxyborohydrideHCID 16743592HCID 16743592, compound

Product 1

HCID 576811018-Chloro-1-iodo-3-[3-(4-methylpiperazin-1-yl)cyclobutyl]imidazo[1,5-a]pyrazine

Procedure

1-Methyl piperazine (5.75 mL, 0.0514 mol) in 1,2-dichloroethane (1096.7 mL, 13.892 mol) was added to 3-(8-chloro-1-iodoimidazo[1,5-a]pyrazin-3-yl)cyclobutanone (17.00 g, 0.04892 mol) and sodium triacetoxyborohydride (21.8 g, 0.0978mol). The reaction stirred at rt for 3 h. The reaction was concentrated, dissolved in CH2Cl2, and then washed with saturated NaHCO3 solution and brine. The product was dried over sodium sulfate, filtered, and concentrated in vacua. The product was flushed through a quick silica gel plug (wetted with 100% CHCl3, eluted with 8% (7N NH3) MeOH in CHCl3), to afford the title compound; NMR (CDCl3, 400 MHz) δ 7.63 (1 H, d), 7.30 (1 H, d), 3.42 (1H, m), 2.94 (1H, m), 2.65 (4 H, m), 2.44 (8 H, m), 2.32 (3H, s); MS (ES+): m/z 431.85/433.87 (100/45) [MH+]; HPLC: tR=1.82 min. (OpenLynx, polar—5 min.).

Workup

  1. concentrationThe reaction was concentrated
  2. dissolutiondissolved in CH2Cl2
  3. washwashed with saturated NaHCO3 solution and brine
  4. dry with materialThe product was dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacua
  7. customThe product was flushed through a quick silica gel plug (wetted with 100% CHCl3, eluted with 8% (7N NH3) MeOH in CHCl3)

Sources & evidence

ORD record
ord-63712d4977824a21ba4525e2294be7f1
Source dataset
uspto-grants-2011_05
Patent number
US07943767B2

Reaction notes

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