Carbon tetrabromide → HCID 67958791, compound

HRID 1478129Notes

Reaction equation

HRID 1478129 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[N:8]1[C:12]([C:13]2[CH:18]=[CH:17][C:16]([O:19][CH2:20][C:21]([F:24])([F:23])[F:22])=[CH:15][N:14]=2)=[N:11][N:10]=[C:9]1[CH:25]=[CH:26][C:27](O)=[O:28].C(Cl)(=O)C(Cl)=O.[C:36]([C:38]1[CH:47]=[CH:46][C:41]([C:42]([NH:44][NH2:45])=O)=[CH:40][CH:39]=1)#[N:37].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(Br)(Br)(Br)Br>ClCCl.C(N(CC)CC)C.CN(C=O)C>[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[N:8]1[C:12]([C:13]2[CH:18]=[CH:17][C:16]([O:19][CH2:20][C:21]([F:24])([F:22])[F:23])=[CH:15][N:14]=2)=[N:11][N:10]=[C:9]1[CH:25]=[CH:26][C:27]1[O:28][C:42]([C:41]2[CH:46]=[CH:47][C:38]([C:36]#[N:37])=[CH:39][CH:40]=2)=[N:44][N:45]=1

Participants

9

Reactant 5

HCID 11205Carbon tetrabromideHCID 11776TriphenylphosphineHCID 65578Oxalyl chlorideHCID 4567324-CyanobenzohydrazideHCID 67960464HCID 67960464, compound

Product 1

HCID 67958791HCID 67958791, compound

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 8471TriethylamineSolvent2×

Conditions

Temperature
-20 °C

Procedure

To a 100 mL flask with 3-{4-(2-Chloro-phenyl)-5-[5-(2,2,2-trifluoro-ethoxy)-pyridin-2-yl]-4H-[1,2,4]triazol-3-yl}-acrylic acid 8 (0.18 g, 0.368 mmol) in dichloromethane (20 mL) was added oxalyl chloride (0.20 g, 1.55 mmol) and a drop of DMF. The reaction was kept at ambient temperature for 3 h. The solvent was removed and the residue was further dried under high vacuum and cooled to −20° C. Dichloromethane (10 mL) was added, followed by 4-Cyano-benzoic acid hydrazide (0.18 g, 1.1 mmol) and triethylamine (0.5 mL). The reaction mixture was kept at this temperature for 0.5 h and then ambient temperature for 1 h. The solvent was removed and the crude 4-Cyano-benzoic acid N′-(3-{4-(2-chloro-phenyl)-5-[5-(2,2,2-trifluoro-ethoxy)-pyridin-2-yl]-4H-[1,2,4]triazol-3-yl}-acryloyl)-hydrazide was used for the next step. 4-Cyano-benzoic acid N′-(3-{4-(2-chloro-phenyl)-5-[5-(2,2,2-trifluoro-ethoxy)-pyridin-2-yl]-4H-[1,2,4]triazol-3-yl}-acryloyl)-hydrazide was dissolved in dichloromethane (10 mL) and triphenylphosphine (0.19 g, 0.736 mmol), carbon tetrabromide (0.24 g, 0.736 mmol) and triethylamine (0.18 mL, 1.30 mmol) were added. The reaction mixture was kept at ambient temperature for 2 h. The final compound was purified by column chromatography (eluting with hexane and ethyl acetate 1:3) to give 4-[5-(2-{4-(2-Chloro-phenyl)-5-[5-(2,2,2-trifluoro-ethoxy)-pyridin-2-yl]-4H-[1,2,4]triazol-3-yl}-vinyl)-[1,3,4]oxadiazol-2-yl]-benzonitrile as a yellow solid. Yield: 0.07 g, 30%.

Workup

  1. customThe solvent was removed
  2. customthe residue was further dried under high vacuum
  3. additionDichloromethane (10 mL) was added
  4. waitThe reaction mixture was kept at this temperature for 0.5 h
  5. waitambient temperature for 1 h
  6. customThe solvent was removed
  7. dissolution4-Cyano-benzoic acid N′-(3-{4-(2-chloro-phenyl)-5-[5-(2,2,2-trifluoro-ethoxy)-pyridin-2-yl]-4H-[1,2,4]triazol-3-yl}-acryloyl)-hydrazide was dissolved in dichloromethane (10 mL)
  8. waitThe reaction mixture was kept at ambient temperature for 2 h
  9. customThe final compound was purified by column chromatography (eluting with hexane and ethyl acetate 1:3)

Sources & evidence

ORD record
ord-2515cf4cf02b4130b5bc3c590bab8e11
Source dataset
uspto-grants-2016_08
Patent number
US09403812B2

Reaction notes

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