Water → 2-iodo-4-(1-methyl piperidin-4-yloxy)-9,10-dihydro-4H-3,10a-diaza-benzo[f]azulene

HRID 1773856Notes

Reaction equation

HRID 1773856 reaction equation
[OH:1][CH:2]1[CH2:7][CH2:6][N:5]([CH3:8])[CH2:4][CH2:3]1.[I:9][C:10]1[N:11]=[C:12]([CH:23]=O)[N:13]([CH2:15][CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[CH:14]=1.O.[OH-].[Na+]>CS(O)(=O)=O.C(Cl)(Cl)Cl>[I:9][C:10]1[N:11]=[C:12]2[N:13]([CH2:15][CH2:16][C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=3[CH:23]2[O:1][CH:2]2[CH2:7][CH2:6][N:5]([CH3:8])[CH2:4][CH2:3]2)[CH:14]=1

Participants

7

Reactant 4

HCID 962WaterHCID 14798Sodium HydroxideHCID 660484-Piperidinol, 1-methyl-HCID 867039454-Iodo-1-phenethyl-imidazole-2-carbaldehyde

Product 1

HCID 726957782-iodo-4-(1-methyl piperidin-4-yloxy)-9,10-dihydro-4H-3,10a-diaza-benzo[f]azulene

Reagents, catalysts & solvents 2

HCID 6212ChloroformSolventHCID 6395Methanesulfonic AcidSolvent

Procedure

To a solution of 4-hydroxy-N-methylpiperidine (223 mg, 2.02 mmoles) in methanesulfonic acid (3.4 mL) is added a solution of 4-Iodo-1-phenethyl-imidazole-2-carbaldehyde (example 2B) (220 mg, 0.675 mmoles) in chloroform (1 mL). The reaction mixture is stirred at room temperature overnight. Water is added to the reaction mixture, and the pH is adjusted to 9-10 by adding 12N NaOH dropwise. The aqueous phase is extracted three times with dichloromethane. The organic phase is dried over magnesium sulphate, filtered and the solvent is removed under reduced pressure. The residue is purified by silica gel chromatography using (CH2Cl2:MeOH:NH4OH) as eluent with a gradient from (99:5:0.1) to (95:5:0.5) to give 2-iodo-4-(1-methylpiperidin-4-yloxy)-9,10-dihydro-4H-3,10a-diaza-benzo[f]azulene melting at 126° C.

Workup

  1. extractionThe aqueous phase is extracted three times with dichloromethane
  2. dry with materialThe organic phase is dried over magnesium sulphate
  3. filtrationfiltered
  4. customthe solvent is removed under reduced pressure
  5. customThe residue is purified by silica gel chromatography

Sources & evidence

ORD record
ord-165bfdb9a482459ea4fd996cae861683
Source dataset
uspto-grants-2016_02
Patent number
US09255101B2

Reaction notes

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