Dabco → (R)-1-(3-(4-((5-(2-(4-chloro-3-methoxyphenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazol-2-ylthio)methyl)-3,5-difluoro-N-(1-methoxy-1-oxopropan-2-yl)phenylsulfonamido)propyl)-4-aza-1-azoniabicyclo[2.2.2]octane bromide

HRID 83848Notes

Reaction equation

HRID 83848 reaction equation
[Br:1][CH2:2][CH2:3][CH2:4][N:5]([C@H:43]([CH3:48])[C:44]([O:46][CH3:47])=[O:45])[S:6]([C:9]1[CH:14]=[C:13]([F:15])[C:12]([CH2:16][S:17][C:18]2[N:19]([C:35]3[CH:40]=[CH:39][C:38]([F:41])=[CH:37][CH:36]=3)[C:20]([C:23]([C:26]3[CH:31]=[CH:30][C:29]([Cl:32])=[C:28]([O:33][CH3:34])[CH:27]=3)([CH3:25])[CH3:24])=[CH:21][N:22]=2)=[C:11]([F:42])[CH:10]=1)(=[O:8])=[O:7].[CH2:49]1[N:54]2[CH2:55][CH2:56][N:51]([CH2:52][CH2:53]2)[CH2:50]1>CC#N>[Br-:1].[Cl:32][C:29]1[CH:30]=[CH:31][C:26]([C:23]([C:20]2[N:19]([C:35]3[CH:40]=[CH:39][C:38]([F:41])=[CH:37][CH:36]=3)[C:18]([S:17][CH2:16][C:12]3[C:13]([F:15])=[CH:14][C:9]([S:6]([N:5]([CH2:4][CH2:3][CH2:2][N+:51]45[CH2:56][CH2:55][N:54]([CH2:53][CH2:52]4)[CH2:49][CH2:50]5)[C@H:43]([CH3:48])[C:44]([O:46][CH3:47])=[O:45])(=[O:8])=[O:7])=[CH:10][C:11]=3[F:42])=[N:22][CH:21]=2)([CH3:25])[CH3:24])=[CH:27][C:28]=1[O:33][CH3:34]

Participants

4

Reactant 2

HCID 9237DabcoHCID 67237163(R)-methyl 2-(N-(3-bromopropyl)-4-((5-(2-(4-chloro-3-methoxyphenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazol-2-ylthio)methyl)-3,5-difluorophenylsulfonamido)propanoate

Product 1

HCID 86702239(R)-1-(3-(4-((5-(2-(4-chloro-3-methoxyphenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazol-2-ylthio)methyl)-3,5-difluoro-N-(1-methoxy-1-oxopropan-2-yl)phenylsulfonamido)propyl)-4-aza-1-azoniabicyclo[2.2.2]octane bromideYield 99%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of (R)-methyl 2-(N-(3-bromopropyl)-4-((5-(2-(4-chloro-3-methoxyphenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazol-2-ylthio)methyl)-3,5-difluorophenylsulfonamido)propanoate (110 mg, 0.14 mol) in MeCN (3 mL) was added DABCO (20 mg, 0.18 mol.). The reaction flask was heated at 60° C. for 3 h. The reaction mixture was cooled to room temperature and concentrated under reduced pressure. Recrystallization of the residue from DCM/Et2O (1:5) gave (R)-1-(3-(4-((5-(2-(4-chloro-3-methoxyphenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazol-2-ylthio)methyl)-3,5-difluoro-N-(1-methoxy-1-oxopropan-2-yl)phenylsulfonamido)propyl)-4-aza-1-azoniabicyclo[2.2.2]octane bromide (118 mg, 99%) as a white solid. 1H NMR (400 MHz, CDCl3) δ 7.33 (d, 2H), 7.17-7.18 (d, 1H), 7.11 (s, 1H), 6.82-6.87 (m, 2H), 6.48-6.55 (m, 4H), 4.51-4.55 (q, 1H), 3.86-3.92 (q, 2H), 3.75 (s, 3H), 3.70 (s, 3H), 3.63-3.66 (t, 8H), 3.38-3.43 (m, 2H), 3.22-3.24 (t, 6H), 2.15-2.34 (m, 2H), 1.52 (s, 6H), 1.50 (s, 3H).

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. concentrationconcentrated under reduced pressure
  3. customRecrystallization of the residue from DCM/Et2O (1:5)

Sources & evidence

ORD record
ord-866c653b6b5c49bcba3afc8133f05e55
Source dataset
uspto-grants-2014_09
Patent number
US08846739B2

Reaction notes

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