Sodium Hydroxide → HCID 44177178, compound

HRID 1673022Notes

Reaction equation

HRID 1673022 reaction equation
[NH2:1][C:2]([CH3:38])([CH3:37])[CH2:3][NH:4][C:5]([C:7]1[N:8]=[C:9]([C:29]2[C:34]([Cl:35])=[CH:33][CH:32]=[CH:31][C:30]=2[Cl:36])[N:10]([C:12]2[CH:17]=[CH:16][C:15]([C:18]3[CH:23]=[CH:22][CH:21]=[C:20]([S:24]([CH3:27])(=[O:26])=[O:25])[CH:19]=3)=[CH:14][C:13]=2[Cl:28])[CH:11]=1)=O.O=P(Cl)(Cl)Cl.O1CCOCC1.[OH-].[Na+]>CCOC(C)=O.O>[Cl:28][C:13]1[CH:14]=[C:15]([C:18]2[CH:23]=[CH:22][CH:21]=[C:20]([S:24]([CH3:27])(=[O:26])=[O:25])[CH:19]=2)[CH:16]=[CH:17][C:12]=1[N:10]1[CH:11]=[C:7]([C:5]2[NH:1][C:2]([CH3:38])([CH3:37])[CH2:3][N:4]=2)[N:8]=[C:9]1[C:29]1[C:34]([Cl:35])=[CH:33][CH:32]=[CH:31][C:30]=1[Cl:36]

Participants

7

Reactant 4

HCID 14798Sodium HydroxideHCID 24813Phosphorus oxychlorideHCID 312751,4-DioxaneHCID 59240199HCID 59240199, compound

Product 1

HCID 44177178HCID 44177178, compoundYield 51%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a N2 purged 100 mL round bottom flask attached with condenser was added 1-(3-Chloro-3′-methanesulfonyl-biphenyl-4-yl)-2-(2,6-dichloro-phenyl)-1H-imidazole-4-carboxylic acid (2-amino-2-methyl-propyl)-amide (590 mg, 1.00 mmol), POCl3 (0.91 mL, 10 mmol) and anhydrous 1,4-dioxane (35 mL). The reaction solution was heated at reflux for 2 hrs. The cooled reaction mixture was added H2O (50 mL) and the mixture as poured to a separatory funnel. To the mixture was added EtOAc (150 mL) and 1N aq. NaOH to raise the pH to 8. The aqueous phase was extracted with EtOAc (70 mL×2), and the combined organic layers were dried over Na2SO4, filtered, concentrated in vacuo, and chromatographed through a 25 g SiO2 column using a gradient of 100% Hexane to 90% EtOAc to afford 288 mg (51% yield) of the title compound. MS (ESI) 573.3, 575.3, 577.2 [M+H]+; 1H NMR (400 MHz, DMSO-d6) δ 11.18 (s, 1H), 9.07 (s, 1H), 8.23 (t, J=2 Hz, 1H), 8.21 (d, J=2 Hz, 1H), 8.11 (d, J=8 Hz, 1H), 7.96 (d, J=8 Hz, 1H), 7.86 (dd, J1=2 Hz, J2=8 Hz, 1H), 7.75 (t, J=8 Hz, 1H), 7.54-7.65 (m, 3H), 7.48 (d, J=8 Hz, 1H), 3.76 (s, 2H), 3.29 (s, 3H), 1.47 (s, 6H).

Workup

  1. customTo a N2 purged 100 mL round bottom flask
  2. customattached with condenser
  3. temperatureThe reaction solution was heated
  4. temperatureat reflux for 2 hrs
  5. customThe cooled reaction mixture
  6. additionthe mixture as poured to a separatory funnel
  7. temperatureto raise the pH to 8
  8. extractionThe aqueous phase was extracted with EtOAc (70 mL×2)
  9. dry with materialthe combined organic layers were dried over Na2SO4
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo
  12. customchromatographed through a 25 g SiO2 column

Sources & evidence

ORD record
ord-2ece5c5d44dd46e0831cc540720d6d8f
Source dataset
uspto-grants-2011_08
Patent number
US07998995B2

Reaction notes

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