Thiophosgene → HCID 25235358, compound

HRID 1360761Notes

Reaction equation

HRID 1360761 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([Cl:8])=[CH:4][N:3]=1.[C:9](Cl)(Cl)=S.[Cl:13][C:14]1[CH:19]=[CH:18][CH:17]=[C:16]([Cl:20])[C:15]=1[C:21]1[NH:22][C:23]2[CH:29]=[C:28]([C:30]([NH:32][NH2:33])=[O:31])[CH:27]=[CH:26][C:24]=2[N:25]=1.CCN=C=NCCCN(C)C>C(Cl)(Cl)Cl.C([O-])(O)=O.[Na+].CCOC(C)=O.CN(C=O)C>[Cl:8][C:5]1[CH:6]=[CH:7][C:2]([NH:1][C:9]2[O:31][C:30]([C:28]3[CH:27]=[CH:26][C:24]4[N:25]=[C:21]([C:15]5[C:16]([Cl:20])=[CH:17][CH:18]=[CH:19][C:14]=5[Cl:13])[NH:22][C:23]=4[CH:29]=3)=[N:32][N:33]=2)=[N:3][CH:4]=1

Participants

9

Reactant 4

HCID 10040ThiophosgeneHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 661742-Amino-5-chloropyridineHCID 577865852-(2,6-Dichloro-phenyl)-3H-benzoimidazole-5-carboxylic acid hydrazide

Product 1

HCID 25235358HCID 25235358, compound

Reagents, catalysts & solvents 4

HCID 6212ChloroformSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolventHCID 516892Sodium BicarbonateSolvent

Procedure

Dissolve 2-amino-5-chloro-pyridine (130 mg, 1.01 mmol) in a biphasic solution of CHCl3 (25 mL) and saturated NaHCO3 (25 mL). Add thiophosgene (46 uL, 0.606 mmol) to the organic phase and stir the reaction vigorously for 2 hr. Add 2-(2,6-dichloro-phenyl)-3H-benzoimidazole-5-carboxylic acid hydrazide (250 mg, 0.778 mmol) and stir overnight. Filter the reaction. Extract the aqueous phase with CHCl3 (25 mL). Concentrate the combined organics and combine with the solid. Evaporate the solvent to yield a yellow solid. Add DMF (3 mL) and EDCI (307 mg, 1.60 mmol) and heat the reaction to 80° C. for 1.5 hr. Allow the reaction to cool to room temp. Dilute with EtOAc (75 mL) and extract with water (15 mL). Dry the organic phase over Na2SO4 and concentrate. Take the concentrate up in DMSO (2 mL) and dilute with water (50 mL). Cool the mixture to 4° C. and collect the precipitate. Recrystallize from toluene/ACN/MeOH to afford the title compound as a cream colored solid: 1H NMR (400 MHz, DMSO-d6) δ ppm 7.62-7.68 (m, 1H) 7.70 (s, 1H) 7.72 (d, J=2.02 Hz, 1H) 7.75-7.85 (m, 1H) 7.85-7.93 (m, 1H) 7.97-8.03 (m, 2H) 8.06 (tautomer, s, 1H) 8.19 (tautomer, s, 1H) 8.39 (dd, J=2.21, 0.95 Hz, 1H) 11.50 (br. s., 1H) 13.30 (br. s., 1H); MS m/z=456.9 (M+1).

Workup

  1. customthe reaction vigorously for 2 hr
  2. filtrationFilter
  3. customthe reaction
  4. extractionExtract the aqueous phase with CHCl3 (25 mL)
  5. concentrationConcentrate the combined organics and
  6. customEvaporate the solvent
  7. customto yield a yellow solid
  8. customthe reaction to 80° C. for 1.5 hr
  9. customthe reaction
  10. extractionextract with water (15 mL)
  11. dry with materialDry the organic phase over Na2SO4
  12. concentrationconcentrate
  13. concentrationconcentrate up in DMSO (2 mL)
  14. additiondilute with water (50 mL)
  15. temperatureCool the mixture to 4° C.
  16. customcollect the precipitate
  17. customRecrystallize from toluene/ACN/MeOH

Sources & evidence

ORD record
ord-b3b939c809f8473ebbe5f63ab228ccc4
Source dataset
uspto-grants-2011_02
Patent number
US07879850B2

Reaction notes

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