Ethylenediamine → HCID 58674351, compound

HRID 1994157Notes

Reaction equation

HRID 1994157 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9](=[O:28])/[C:10](/[CH3:27])=[CH:11]/[C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([O:18][C:19]3[CH:24]=[CH:23][N:22]=[C:21]([C:25]#[N:26])[CH:20]=3)[CH:13]=2)=[CH:4][C:3]=1[C:29]([F:32])([F:31])[F:30].[CH2:33](N)[CH2:34][NH2:35]>C(O)C.CCOC(C)=O>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9](=[O:28])/[C:10](/[CH3:27])=[CH:11]/[C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([O:18][C:19]3[CH:24]=[CH:23][N:22]=[C:21]([C:25]4[NH:35][CH2:34][CH2:33][N:26]=4)[CH:20]=3)[CH:13]=2)=[CH:4][C:3]=1[C:29]([F:32])([F:30])[F:31]

Participants

5

Reactant 2

HCID 3301EthylenediamineHCID 58674598HCID 58674598, compound

Product 1

HCID 58674351HCID 58674351, compound

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 8857Ethyl AcetateSolvent2×

Procedure

(E)-N-(4-Chloro-3-(trifluoromethyl)phenyl)-3-(3-(2-cyanopyridin-4-yloxy)phenyl)-2-methylacrylamide (500 mg, 1.09 mmol) and TEA (456 μL, 3.27 mmol) were combined and stirred in ethanol. H2S was bubbled into the solution for 2 min then the reaction mixture was sealed and allowed to stir at rt. Reaction completion was checked by LCMS and TLC. The mixture was diluted with EtOAc and washed with brine. The aqueous phase was extracted with EtOAc, and the organic solutions were combined, dried over Na2SO4, filtered, and concentrated to provide a yellow residue. The residue was redissolved in ethylene diamine (3 mL), heated to 60° C. for 5 min, and then allowed to cool to rt. The mixture was diluted with EtOAc and washed with brine. The aqueous phase was extracted with EtOAc, and the organic solutions were combined, dried over Na2SO4, filtered, and concentrated. Purification by column chromatography (SiO2, 0-10% MeOH with 1% NH4OH in DCM) provided B-12 (415 mg). LCMS, FA: Rt=1.34 min, [MH+ 501.0]. 1H NMR (400 MHz, CD3OD): δ 8.49 (d, 1H), 8.18 (d, 1H), 7.91-7.89 (dd, 1H), 7.57-7.53 (m, 3H), 7.40 (d, 1H), 7.35 (s, 1H), 7.23 (m, 1H), 7.16-7.13 (dd, 1H), 7.09-7.07 (m, 1H), 3.77 (s, 4H), and 2.16 (d, 3H).

Workup

  1. customH2S was bubbled into the solution for 2 min
  2. customthe reaction mixture was sealed
  3. customReaction completion
  4. washwashed with brine
  5. extractionThe aqueous phase was extracted with EtOAc
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customto provide a yellow residue
  10. temperatureheated to 60° C. for 5 min
  11. temperatureto cool to rt
  12. washwashed with brine
  13. extractionThe aqueous phase was extracted with EtOAc
  14. dry with materialdried over Na2SO4
  15. filtrationfiltered
  16. concentrationconcentrated
  17. customPurification by column chromatography (SiO2, 0-10% MeOH with 1% NH4OH in DCM)
  18. customprovided B-12 (415 mg)

Sources & evidence

ORD record
ord-f93415658df142c6a0fdc6f43a7ce5c1
Source dataset
uspto-grants-2010_01
Patent number
US07652041B2

Reaction notes

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