Thiophosgene → HCID 25235305, compound

HRID 1360760Notes

Reaction equation

HRID 1360760 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([F:11])([F:10])[F:9])=[CH:4][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>[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:7]=[CH:6][C:5]([C:8]([F:9])([F:11])[F:10])=[CH:4][N:3]=4)=[N:36][N:35]=3)[CH:30]=[CH:29][C:27]=2[N:28]=1

Participants

8

Reactant 4

HCID 10040ThiophosgeneHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 7358622-Amino-5-(trifluoromethyl)pyridineHCID 577865852-(2,6-Dichloro-phenyl)-3H-benzoimidazole-5-carboxylic acid hydrazide

Product 1

HCID 25235305HCID 25235305, compound

Reagents, catalysts & solvents 3

HCID 6212ChloroformSolventHCID 8857Ethyl AcetateSolventHCID 516892Sodium BicarbonateSolvent

Procedure

Dissolve 2-amino-5-trifluoromethyl-pyridine (164 mg, 1.01 mmol) in a biphasic solution of CHCl3 (25 mL) and saturated NaHCO3 (25 mL). Add thiophosgene (78 uL, 1.01 mmol) to the organic phase and stir the reaction vigorously for 2.5 hr. Separate the phases and extract the aqueous phase with CHCl3 (25 mL). Concentrate the combined organics and take the concentrate up in DMF (3 mL). Add 2-(2,6-dichloro-phenyl)-3H-benzoimidazole-5-carboxylic acid hydrazide (250 mg, 0.778 mmol) and stir overnight. Add EDCI (298 mg, 1.56 mmol) and heat to 80° C. for 4 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 (35-50% ACN/H2O+5 mM NH4OH) to afford the title compound as a cream colored solid: 1H NMR (400 MHz, DMSO-d6) δ ppm 7.63-7.68 (m, 1H) 7.70 (s, 1H) 7.72 (d, J=1.77 Hz, 1H) 7.76-7.87 (m, 1H) 7.88-7.94 (m, 1H) 8.04-8.30 (m, 3H) 8.72 (br. s., 1H) 11.87 (br. s., 1H) 13.31 (br. s., 1H); MS m/z=491.8 (M+1).

Workup

  1. customthe reaction vigorously for 2.5 hr
  2. customSeparate the phases
  3. extractionextract the aqueous phase with CHCl3 (25 mL)
  4. concentrationConcentrate the combined organics and
  5. concentrationconcentrate up in DMF (3 mL)
  6. additiondilute
  7. extractionextract with water (15 mL)
  8. dry with materialDry the organic phase over Na2SO4
  9. concentrationconcentrate
  10. customPurify the
  11. concentrationconcentrate by reverse phase HPLC (35-50% ACN/H2O+5 mM NH4OH)

Sources & evidence

ORD record
ord-fc5ea40eab25425386c6f0f0157dfd2c
Source dataset
uspto-grants-2011_02
Patent number
US07879850B2

Reaction notes

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