Thiophosgene → HCID 25235359, compound

HRID 1360762Notes

Reaction equation

HRID 1360762 reaction equation
[NH2:1][C:2]1[CH:11]=[CH:10][C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[N:3]=1.[C:12](Cl)(Cl)=S.[Cl:16][C:17]1[CH:22]=[CH:21][CH:20]=[C:19]([Cl:23])[C:18]=1[C:24]1[NH:25][C:26]2[CH:32]=[C:31]([C:33]([NH:35][NH2:36])=[O:34])[CH:30]=[CH:29][C:27]=2[N:28]=1.CCN=C=NCCCN(C)C>C(Cl)(Cl)Cl.C([O-])(O)=O.[Na+].CCOC(C)=O.CN(C=O)C>[Cl:16][C:17]1[CH:22]=[CH:21][CH:20]=[C:19]([Cl:23])[C:18]=1[C:24]1[NH:25][C:26]2[CH:32]=[C:31]([C:33]3[O:34][C:12]([NH:1][C:2]4[CH:11]=[CH:10][C:9]5[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=5)[N:3]=4)=[N:36][N:35]=3)[CH:30]=[CH:29][C:27]=2[N:28]=1

Participants

9

Reactant 4

HCID 10040ThiophosgeneHCID 113792-AminoquinolineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 577865852-(2,6-Dichloro-phenyl)-3H-benzoimidazole-5-carboxylic acid hydrazide

Product 1

HCID 25235359HCID 25235359, compound

Reagents, catalysts & solvents 4

HCID 6212ChloroformSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolventHCID 516892Sodium BicarbonateSolvent

Conditions

Temperature
80 °C

Procedure

Dissolve 2-amino-quinoline (88 mg, 0.607 mmol) in a biphasic solution of CHCl3 (15 mL) and saturated NaHCO3 (15 mL). Add thiophosgene (47 uL, 0.607 mmol) to the organic phase and stir the reaction vigorously for 3 hr. Add 2-(2,6-dichloro-phenyl)-3H-benzoimidazole-5-carboxylic acid hydrazide (150 mg, 0.467 mmol) and stir overnight. Filter the reaction. Extract the aqueous phase with CHCl3 (20 mL). Concentrate the combined organics and combine with the solid. Evaporate the solvent. Add EDCI (96 mg, 0.500 mmol) and DMF (3 mL). Heat to 80° C. for 1 hr. Upon cooling to room temp dilute the reaction with EtOAc (75 mL) and extract with water (15 mL). Dry the organic phase over Na2SO4 and concentrate. Purify the concentrate by reverse phase HPLC (35-65% ACN/H2O+5 mM NH4OH) to afford the title compound as a yellow solid: 1H NMR (400 MHz, MeOD) δ ppm 7.19 (br. s., 1H) 7.45 (m, 1H) 7.55-7.64 (m, 3H) 7.69-7.75 (m, 2H) 7.82 (d, J=7.83 Hz, 2H) 8.05 (dd, J=8.46, 1.52 Hz, 1H) 8.16 (d, J=9.35 Hz, 1H) 8.32 (br. s., 1H); MS m/z=473.0 (M+1).

Workup

  1. customthe reaction vigorously for 3 hr
  2. filtrationFilter
  3. customthe reaction
  4. extractionExtract the aqueous phase with CHCl3 (20 mL)
  5. concentrationConcentrate the combined organics and
  6. customEvaporate the solvent
  7. temperatureUpon cooling to room temp
  8. additiondilute
  9. extractionextract with water (15 mL)
  10. dry with materialDry the organic phase over Na2SO4
  11. concentrationconcentrate
  12. customPurify the
  13. concentrationconcentrate by reverse phase HPLC (35-65% ACN/H2O+5 mM NH4OH)

Sources & evidence

ORD record
ord-9b4eb789e3954e80af3451f0dec89a6d
Source dataset
uspto-grants-2011_02
Patent number
US07879850B2

Reaction notes

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