Piperidine → HCID 86732742, compound

HRID 525875Notes

Reaction equation

HRID 525875 reaction equation
[CH2:1]([N:3]1[C:12]2[C:7](=[CH:8][C:9]([O:23][CH2:24][C:25]3[CH:30]=[CH:29][C:28]([O:31][CH3:32])=[CH:27][CH:26]=3)=[C:10]([O:13][CH2:14][C:15]3[CH:20]=[CH:19][C:18]([O:21][CH3:22])=[CH:17][CH:16]=3)[CH:11]=2)[C:6](=[O:33])[C:5]([CH2:34]O)=[N:4]1)[CH3:2].CS(Cl)(=O)=O.[NH:41]1[CH2:46][CH2:45][CH2:44][CH2:43][CH2:42]1>ClCCl>[CH2:1]([N:3]1[C:12]2[C:7](=[CH:8][C:9]([O:23][CH2:24][C:25]3[CH:26]=[CH:27][C:28]([O:31][CH3:32])=[CH:29][CH:30]=3)=[C:10]([O:13][CH2:14][C:15]3[CH:16]=[CH:17][C:18]([O:21][CH3:22])=[CH:19][CH:20]=3)[CH:11]=2)[C:6](=[O:33])[C:5]([CH2:34][N:41]2[CH2:46][CH2:45][CH2:44][CH2:43][CH2:42]2)=[N:4]1)[CH3:2]

Participants

5

Reactant 3

HCID 8082PiperidineHCID 31297Methanesulfonyl chlorideHCID 86732738HCID 86732738, compound

Product 1

HCID 86732742HCID 86732742, compoundYield 57%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a suspension of 1-ethyl-3-(hydroxymethyl)-6,7-bis((4-methoxybenzyl)oxy)cinnolin-4(1H)-one (Example 8d) (2.13 g, 4.47 mmol) in Dichloromethane (DCM) (40 mL) in an ice bath under N2 was added TEA (1.495 mL, 10.73 mmol) followed by methanesulfonyl chloride (0.627 mL, 8.05 mmol) (white suspension turned into a light yellow clear solution). The mixture was stirred in an ice bath for 2 h, and then the above reaction mixture was added dropwise into a stirred solution of piperidine (1.195 mL, 12.07 mmol) in dichloromethane (DCM) (40.0 mL) at room temperature overnight. The reaction mixture was concentrated and purified through column chromatography eluting with dichloromethane and methanol/dichloromethane/ammonium hydroxide (from 0% to 100%) over 15 mins twice to afford 1-ethyl-6,7-bis((4-methoxybenzyl)oxy)-3-(piperidin-1-ylmethyl)cinnolin-4(1H)-one (1.54 g, 2.55 mmol, 57.0% yield). LCMS (M+H)+: 544.0

Workup

  1. concentrationThe reaction mixture was concentrated
  2. custompurified through column chromatography
  3. washeluting with dichloromethane and methanol/dichloromethane/ammonium hydroxide (from 0% to 100%) over 15 mins twice

Sources & evidence

ORD record
ord-ce890a0f6ec446bab938b2dbd449f133
Source dataset
uspto-grants-2016_05
Patent number
US09340556B2

Reaction notes

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