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

HRID 448972Notes

Reaction equation

HRID 448972 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 (1700 g, 0.04892 mol) and sodium triacetoxyborohydride (21.8 g, 0.0978 mol). 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 vacuo. 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; 1H NMR (CDCl3, 400 MHz) δ 7.63 (1H, d), 7.30 (1H, d), 3.42 (1H, m), 2.94 (1H, m), 2.65 (4H, m), 2.44 (8H, 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 vacuo
  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-fadc716a572a48d496b2ec518137d1fe
Source dataset
uspto-grants-2013_07
Patent number
US08481733B2

Reaction notes

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