1,4-Dioxane hydrochloride → HCID 136128343, compound

HRID 220867Notes

Reaction equation

HRID 220867 reaction equation
C(OC([N:8]1[CH2:13][CH2:12][N:11]([C:14](=[O:41])[CH2:15][CH2:16][C:17]2[CH:22]=[CH:21][C:20]([C:23]([N:25]3[CH2:34][C:33]4[CH:32]=[N:31][N:30]([CH3:35])[C:29]=4[NH:28][C:27]4[CH:36]=[CH:37][CH:38]=[CH:39][C:26]3=4)=[O:24])=[CH:19][C:18]=2[CH3:40])[CH2:10][CH2:9]1)=O)(C)(C)C.Cl.O1CCOCC1>CO>[CH3:40][C:18]1[CH:19]=[C:20]([C:23]([N:25]2[CH2:34][C:33]3[CH:32]=[N:31][N:30]([CH3:35])[C:29]=3[NH:28][C:27]3[CH:36]=[CH:37][CH:38]=[CH:39][C:26]2=3)=[O:24])[CH:21]=[CH:22][C:17]=1[CH2:16][CH2:15][C:14]([N:11]1[CH2:10][CH2:9][NH:8][CH2:13][CH2:12]1)=[O:41]

Participants

4

Reactant 2

HCID 204431481,4-Dioxane hydrochlorideHCID 136128420HCID 136128420, compound

Product 1

HCID 136128343HCID 136128343, compoundYield 73%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

4-{3-[2-Methyl-4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-phenyl]-propionyl}-piperazine-1-carboxylic acid tert-butyl ester from Example E47.1 (1.09 g, 1.95 mmol) was dissolved in methanol (20 ml) and 4M HCl/dioxan solution (20 ml) was added. The mixture was stirred for 3 h at room temperature, concentrated in vacuo and azeotroped with toluene. The residue was dissolved in methanol (30 ml) and ammonia (5 ml) then concentrated in vacuo. The residue was purified by flash chromatography on silica gel (eluant; 0.5% 35% ammonia:4.5% methanol:95% dichloro-methane to 1% 35% ammonia:9% methanol:90% dichloro-methane) to yield the title compound (759 mg, 73%).

Workup

  1. concentrationconcentrated in vacuo
  2. customazeotroped with toluene
  3. dissolutionThe residue was dissolved in methanol (30 ml)
  4. concentrationammonia (5 ml) then concentrated in vacuo
  5. customThe residue was purified by flash chromatography on silica gel (eluant; 0.5% 35% ammonia:4.5% methanol:95% dichloro-methane to 1% 35% ammonia:9% methanol:90% dichloro-methane)

Sources & evidence

ORD record
ord-2eea194255fd406895bbaeaf46048ebc
Source dataset
uspto-grants-2012_06
Patent number
US08202858B2

Reaction notes

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