1-Chloro-4-(chloromethyl)benzene → 4-{2-[3-(1-tert-Butoxycarbonylmethyl-piperidin-4-yl)-1-(4-chloro-benzyl)-1H-indazol-6-yl]-ethyl}-piperidine-1carboxylic acid tert-butyl ester

HRID 343414Notes

Reaction equation

HRID 343414 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([CH2:14][CH2:15][C:16]2[CH:24]=[C:23]3[C:19]([C:20]([CH:25]4[CH2:30][CH2:29][N:28]([CH2:31][C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])[CH2:27][CH2:26]4)=[N:21][NH:22]3)=[CH:18][CH:17]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].[Cl:41][C:42]1[CH:49]=[CH:48][C:45]([CH2:46]Cl)=[CH:44][CH:43]=1>CN(C=O)C>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([CH2:14][CH2:15][C:16]2[CH:24]=[C:23]3[C:19]([C:20]([CH:25]4[CH2:26][CH2:27][N:28]([CH2:31][C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])[CH2:29][CH2:30]4)=[N:21][N:22]3[CH2:46][C:45]3[CH:48]=[CH:49][C:42]([Cl:41])=[CH:43][CH:44]=3)=[CH:18][CH:17]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 77231-Chloro-4-(chloromethyl)benzeneHCID 24758Sodium hydrideHCID 178451207HCID 178451207, compound

Product 1

HCID 540299254-{2-[3-(1-tert-Butoxycarbonylmethyl-piperidin-4-yl)-1-(4-chloro-benzyl)-1H-indazol-6-yl]-ethyl}-piperidine-1carboxylic acid tert-butyl esterYield 35%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

A solution of 4-{2-[3-(l-tert-butoxycarbonylmethyl-piperidin-4-yl)-1H-indazol-6-yl]-ethyl}-piperidine-1carboxylic acid tert-butyl ester (0.25 g, 0.475 mmol) in dry DMF (5 ml) was treated with sodium hydride (0.021 g, 0.523 mmol, 60% dispersion in oil) and the mixture was stirred at 23° under nitrogen for 30 min. A solution of 4-chlorobenzyl chloride (0.080 g, 0.497 mmol; Aldrich) in DMF (5 ml) was added and the mixture was stirred at 23° for 20 h. The solvent was removed in vacuo, the residue treated with water and extracted with dichloromethane (3×30 ml); the extracts were evaporated in vacuo to give an orange gum. Purification by flash chromatography on silica gel (Merck 9385), eluant ether: cyclohexane:triethylamine (50:50:2 to 100:0:2), gave the title compound as a colourless gum (0.107 g, 35%).

Workup

  1. stirringthe mixture was stirred at 23° for 20 h
  2. customThe solvent was removed in vacuo
  3. additionthe residue treated with water
  4. extractionextracted with dichloromethane (3×30 ml)
  5. customthe extracts were evaporated in vacuo
  6. customto give an orange gum
  7. customPurification by flash chromatography on silica gel (Merck 9385), eluant ether: cyclohexane:triethylamine (50:50:2 to 100:0:2)

Sources & evidence

ORD record
ord-2e6368cb5132431989dc147295d0ab16
Source dataset
uspto-grants-1999_01
Patent number
US05861414

Reaction notes

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