Trifluoroacetic acid → HCID 59177899, compound

HRID 1661117Notes

Reaction equation

HRID 1661117 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:9]([NH:35][NH:36][C:37](=O)[CH2:38][NH:39]C(=O)OC(C)(C)C)=[N:10][N:11]([CH2:23][C:24]3[C:25]([CH3:34])=[N:26][C:27]([C:30]([F:33])([F:32])[F:31])=[CH:28][CH:29]=3)[C:12](=[O:22])[C:13]=2[C:14]2[CH:19]=[CH:18][C:17]([C:20]#[N:21])=[CH:16][CH:15]=2)=[CH:4][CH:3]=1.ClC(Cl)(Br)C(Cl)(Cl)Br.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CCN(CC)CC.C(O)(C(F)(F)F)=O>CCOC(C)=O.C(Cl)Cl.CO.C(Cl)Cl.C(#N)C>[NH2:39][CH2:38][C:37]1[N:10]2[N:11]([CH2:23][C:24]3[C:25]([CH3:34])=[N:26][C:27]([C:30]([F:32])([F:33])[F:31])=[CH:28][CH:29]=3)[C:12](=[O:22])[C:13]([C:14]3[CH:19]=[CH:18][C:17]([C:20]#[N:21])=[CH:16][CH:15]=3)=[C:8]([C:5]3[CH:4]=[CH:3][C:2]([Cl:1])=[CH:7][CH:6]=3)[C:9]2=[N:35][N:36]=1

Participants

10

Reactant 5

HCID 6422Trifluoroacetic acidHCID 8471TriethylamineHCID 11776TriphenylphosphineHCID 694261,2-Dibromo-1,1,2,2-tetrachloroethaneHCID 67129301HCID 67129301, compound

Product 1

HCID 59177899HCID 59177899, compoundYield 34%

Reagents, catalysts & solvents 4

HCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolventHCID 21226129Dichloromethane methanolSolvent

Conditions

Temperature
0 °C

Procedure

To a round bottom flask was added tert-butyl 2-(2-(4-(4-chlorophenyl) -5-(4-cyanophenyl)-1-((2-methyl-6-(trifluoromethyl)pyridin-3-yl)methyl)-6-oxo-1,6-dihydropyridazin-3-yl)hydrazinyl)-2-oxoethylcarbamate (54 mg, 0.0808 mmol), acetonitrile (3 ml), and tetra-chloro-1,2-dibromo-ethane (58 mg, 0.178 mmol). The reaction was cooled to 0° C. Triphenylphosphine (47 mg, 0.178 mmol) was then added and the reaction was stirred at 0° C. for 5 min. After this time, Et3N (0.05 ml, 0.356 mmol) was added to the reaction. The reaction was slowly warmed up to rt and stirred for 16 hrs. After this time, the reaction was diluted with EtOAc (25 ml). The resulting solution was washed with water (2×20 ml) and saturated NaCl (20 ml). The organic layer was dried over MgSO4, filtered and concentrated. The crude product was purified by silica gel column chromatography (8 gm silica gel) eluting with a gradient of 20%-80% EtOAc/Hex to give the cyclized intermediate. This material was then dissolved in CH2Cl2(1 ml) and TFA (1 ml) was added. The reaction was stirred at rt for 1 hr. After this time, the solvent was removed. The residue was diluted with EtOAc (20 ml). The resulting solution was washed with saturated NaHCO3(20 ml), water (10 ml) and saturated NaCl (10 ml). The organic layer was dried over MgSO4, filtered and concentrated. The crude product was purified by silica gel column chromatography (4 g silica gel) eluting with a gradient of 100% EtOAc and then 5% MeOH/CH2Cl2 to give product as a white solid (15 mg, 34% yield).

Workup

  1. temperatureThe reaction was slowly warmed up to rt
  2. stirringstirred for 16 hrs
  3. washThe resulting solution was washed with water (2×20 ml) and saturated NaCl (20 ml)
  4. dry with materialThe organic layer was dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude product was purified by silica gel column chromatography (8 gm silica gel)
  8. washeluting with a gradient of 20%-80% EtOAc/Hex
  9. customto give the cyclized intermediate
  10. stirringThe reaction was stirred at rt for 1 hr
  11. customAfter this time, the solvent was removed
  12. additionThe residue was diluted with EtOAc (20 ml)
  13. washThe resulting solution was washed with saturated NaHCO3(20 ml), water (10 ml) and saturated NaCl (10 ml)
  14. dry with materialThe organic layer was dried over MgSO4
  15. filtrationfiltered
  16. concentrationconcentrated
  17. customThe crude product was purified by silica gel column chromatography (4 g silica gel)
  18. washeluting with a gradient of 100% EtOAc

Sources & evidence

ORD record
ord-b99e789be107427d81777a67e2316d8b
Source dataset
uspto-grants-2011_10
Patent number
US08030306B2

Reaction notes

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