Potassium Carbonate → 3-(N-(4-carboxybenzyl)-4-((5-(2-(4-chloro-3-methoxyphenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazol-2-ylthio)methyl)-3,5-difluorophenylsulfonamido)-N,N,N-trimethylpropan-1-aminium chloride

HRID 83835Notes

Reaction equation

HRID 83835 reaction equation
[Cl-].[Cl:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]([C:12]2[N:16]([C:17]3[CH:22]=[CH:21][C:20]([F:23])=[CH:19][CH:18]=3)[C:15]([S:24][CH2:25][C:26]3[C:31]([F:32])=[CH:30][C:29]([S:33]([NH:36][CH2:37][CH2:38][CH2:39][N+:40]([CH3:43])([CH3:42])[CH3:41])(=[O:35])=[O:34])=[CH:28][C:27]=3[F:44])=[N:14][CH:13]=2)([CH3:11])[CH3:10])=[CH:5][C:4]=1[O:45][CH3:46].[C:47]([O-:50])([O-])=[O:48].[K+].[K+]>CN(C=O)C>[Cl-:2].[C:47]([C:3]1[CH:8]=[CH:7][C:6]([CH2:9][N:36]([CH2:37][CH2:38][CH2:39][N+:40]([CH3:41])([CH3:43])[CH3:42])[S:33]([C:29]2[CH:28]=[C:27]([F:44])[C:26]([CH2:25][S:24][C:15]3[N:16]([C:17]4[CH:22]=[CH:21][C:20]([F:23])=[CH:19][CH:18]=4)[C:12]([C:9]([C:6]4[CH:7]=[CH:8][C:3]([Cl:2])=[C:4]([O:45][CH3:46])[CH:5]=4)([CH3:10])[CH3:11])=[CH:13][N:14]=3)=[C:31]([F:32])[CH:30]=2)(=[O:35])=[O:34])=[CH:5][CH:4]=1)([OH:50])=[O:48]

Participants

4

Reactant 2

HCID 11430Potassium CarbonateHCID 67238046HCID 67238046, compound

Product 1

HCID 672370063-(N-(4-carboxybenzyl)-4-((5-(2-(4-chloro-3-methoxyphenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazol-2-ylthio)methyl)-3,5-difluorophenylsulfonamido)-N,N,N-trimethylpropan-1-aminium chlorideYield 187.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 3-(4-((5-(2-(4-chloro-3-methoxyphenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazol-2-ylthio)methyl)-3,5-difluorphenylsulfonamido)-N,N,N-trimethylpropan-1-aminium chloride (96 mg, 0.13 mmol) in DMF (2 mL) was added K2CO3 (80 mg, 0.58 mmol) and methyl-(4-bromomethyl)-benzoate (40 mg, 0.18 mmol) at 25° C. and the resulting suspension was stirred for 24 h. The reaction mixture was quenched into water (20 mL) and extracted with EtOAc (3×20 mL). The combined organic layers were washed with brine (20 mL), dried over MgSO4 and concentrated to a colorless oil. The oil was reconstituted in THF (6 mL) and added to a solution of LiOH.H2O (420 mg) in water (10 mL) at 25° C. After 30 min the reaction was concentrated and adjusted to pH 1 with conc HCl. The aqueous layer was extracted with DCM, and combined extracts were dried (MgSO4) and concentrated to furnish the title product (104 mg, 95%) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ 7.94 (d, J=8.2 Hz, 2H), 7.62 (d, J=6.4 Hz, 2H), 7.48 (d, J=8.2 Hz, 2H), 7.25 (d, J=8.3 Hz, 1H), 7.18 (s, 1H), 7.01 (t, J=8.7 Hz, 2H), 6.61 (dd, J=8.8, 4.9 Hz, 2H), 6.55 (d, J=1.8 Hz, 1H), 6.50 (dd, J=8.3, 1.9 Hz, 1H), 4.51 (s, 2H), 4.02 (s, 2H), 3.68 (s, 3H), 3.28-3.14 (m, 2H), 3.14-3.04 (m, 2H), 2.92 (s, 9H), 1.67 (d, J=8.3 Hz, 2H), 1.47 (s, 6H); MS (EI) m/z 815 (MH+).

Workup

  1. customThe reaction mixture was quenched into water (20 mL)
  2. extractionextracted with EtOAc (3×20 mL)
  3. washThe combined organic layers were washed with brine (20 mL)
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated to a colorless oil
  6. additionadded to a solution of LiOH.H2O (420 mg) in water (10 mL) at 25° C
  7. concentrationAfter 30 min the reaction was concentrated
  8. extractionThe aqueous layer was extracted with DCM
  9. dry with materialwere dried (MgSO4)
  10. concentrationconcentrated

Sources & evidence

ORD record
ord-5a26d7c89e63421daf6a3ef472bf3879
Source dataset
uspto-grants-2014_09
Patent number
US08846739B2

Reaction notes

Loading…