Potassium Carbonate → 2-(difluoromethyl)-1-(4,6-di-8-oxa-3-azabicyclo[3.2.1]oct-3-yl-1,3,5-triazin-2-yl)-1H-benzimidazole

HRID 404481Notes

Reaction equation

HRID 404481 reaction equation
Cl[C:2]1[N:7]=[C:6]([N:8]2[CH2:14][CH:13]3[O:15][CH:10]([CH2:11][CH2:12]3)[CH2:9]2)[N:5]=[C:4]([N:16]2[CH2:22][CH:21]3[O:23][CH:18]([CH2:19][CH2:20]3)[CH2:17]2)[N:3]=1.[F:24][CH:25]([F:35])[C:26]1[NH:30][C:29]2[CH:31]=[CH:32][CH:33]=[CH:34][C:28]=2[N:27]=1.C([O-])([O-])=O.[K+].[K+].Cl.C12OC(CC1)CNC2>CN(C=O)C>[F:35][CH:25]([F:24])[C:26]1[N:27]([C:2]2[N:3]=[C:4]([N:16]3[CH2:22][CH:21]4[O:23][CH:18]([CH2:19][CH2:20]4)[CH2:17]3)[N:5]=[C:6]([N:8]3[CH2:9][CH:10]4[O:15][CH:13]([CH2:12][CH2:11]4)[CH2:14]3)[N:7]=2)[C:28]2[CH:34]=[CH:33][CH:32]=[CH:31][C:29]=2[N:30]=1

Participants

6

Reactant 4

HCID 11430Potassium CarbonateHCID 5977032-(difluoromethyl)-1H-1,3-benzodiazoleHCID 219835368-Oxa-3-aza-bicyclo(3.2.1)octane hydrochlorideHCID 579982733,3'-(6-Chloro-1,3,5-triazine-2,4-diyl)bis(8-oxa-3-azabicyclo[3.2.1]octane)

Product 1

HCID 468847822-(difluoromethyl)-1-(4,6-di-8-oxa-3-azabicyclo[3.2.1]oct-3-yl-1,3,5-triazin-2-yl)-1H-benzimidazole

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of cyanuric chloride (922 mg, 5 mmol) in acetone (5 mL) was added to ice. A solution of 8-oxa-3-azabicyclo[3.2.1]octane hydrochloride (750 mg, 5 mmol) and triethylamine (2.1 mL, 15 mmol) in aqueous acetone was then added. After 20 min the precipitate was collected to give 1.0 g of a white powder which was a 7:3 mixture of 3-(4,6-dichloro-1,3,5-triazine-2,4-diyl)-8-oxa-3-azabicyclo[3.2.1]octane and 3,3′-(6-chloro-1,3,5-triazine-2,4-diyl)bis(8-oxa-3-azabicyclo[3.2.1]octane). Treatment of the mixture (400 mg) with 2-(difluoromethyl)-1H-benzo[d]imidazole (146 mg, 0.87 mmol) and K2CO3 (967 mg, 7 mmol) in DMF (2.5 mL) for 18 hours, followed by addition of 8-oxa-3-azabicyclo[3.2.1]octane hydrochloride (150 mg) gave, after 1 h, 3,3′-(6-(2-(difluoromethyl)-1H-benzo[d]imidazol-1-yl)-1,3,5-triazine-2,4-diyl)bis(8-oxa-3-azabicyclo[3.2.1]octane) after purification by HPLC. (M+H) 475.

Workup

  1. customgave, after 1 h
  2. custom3,3′-(6-(2-(difluoromethyl)-1H-benzo[d]imidazol-1-yl)-1,3,5-triazine-2,4-diyl)bis(8-oxa-3-azabicyclo[3.2.1]octane) after purification by HPLC

Sources & evidence

ORD record
ord-9db5b38b148a4eb386b15ce5aa42e45b
Source dataset
uspto-grants-2014_06
Patent number
US08748421B2

Reaction notes

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