Trifluoroacetic acid → HCID 46830039, compound

HRID 1803231Notes

Reaction equation

HRID 1803231 reaction equation
[CH2:1]([N:4]1[C:8]([CH:9]([C:13]2[CH:18]=[CH:17][C:16]([F:19])=[CH:15][CH:14]=2)[CH2:10][CH:11]=C)=[N:7][C:6]([NH:20][C:21]2[CH:26]=[CH:25][C:24]([N:27]3[CH:31]=[C:30]([Cl:32])[N:29]=[CH:28]3)=[C:23]([O:33][CH3:34])[CH:22]=2)=[N:5]1)[CH:2]=C.C(O)(C(F)(F)F)=O>CC1C=C(C)C(N2C(=[Ru](Cl)(Cl)=CC3C=CC=CC=3OC(C)C)N(C3C(C)=CC(C)=CC=3C)CC2)=C(C)C=1.ClCCCl>[Cl:32][C:30]1[N:29]=[CH:28][N:27]([C:24]2[CH:25]=[CH:26][C:21]([NH:20][C:6]3[N:7]=[C:8]4[CH:9]([C:13]5[CH:14]=[CH:15][C:16]([F:19])=[CH:17][CH:18]=5)[CH2:10][CH:11]=[CH:2][CH2:1][N:4]4[N:5]=3)=[CH:22][C:23]=2[O:33][CH3:34])[CH:31]=1

Participants

5

Reactant 2

HCID 6422Trifluoroacetic acidHCID 66858922HCID 66858922, compound

Product 1

HCID 46830039HCID 46830039, compoundYield 13%

Reagents, catalysts & solvents 2

HCID 11763533(1,3-Bis(2,4,6-trimethylphenyl)imidazolidin-2-ylidene)(dichloro)((2-((propan-2-yl)oxy)phenyl)methylidene)rutheniumCatalyst2×HCID 111,2-DichloroethaneSolvent

Conditions

Temperature
70 °C

Procedure

Hoveyda-Grubbs Catalyst 2nd Generation (109 mg, 0.173 mmol) was added to a solution of 1-allyl-N-(4-(4-chloro-1H-imidazol-1-yl)-3-methoxyphenyl)-5-(1-(4-fluorophenyl)but-3-enyl)-1H-1,2,4-triazol-3-amine, TFA (410 mg, 0.691 mmol) in DCE (50.0 mL). The flask was flushed with nitrogen, sealed, and heated at 70° C. for 72 h. The reaction mixture was cooled to rt and an additional portion of Hoveyda-Grubbs Catalyst 2nd Generation (109 mg, 0.173 mmol) was added. The mixture was flushed with nitrogen, sealed, and heated at 70° C. for an additional 24 h. The crude reaction contents were directly loaded onto silica gel and the product was purified using silica gel column chromatography (10-75% EtOAc/chloroform, linear gradient) to afford (Z)—N-(4-(4-chloro-1H-imidazol-1-yl)-3-methoxyphenyl)-9-(4-fluorophenyl)-8,9-dihydro-5H-[1,2,4]triazolo[1,5-a]azepin-2-amine (40 mg, 13% yield) as a solid. LC-MS (M+H)+ 451.1. 1H NMR (500 MHz, chloroform-d) δ ppm 7.52 (d, J=1.53 Hz, 1 H) 7.40 (d, J=2.14 Hz, 1 H) 7.24 (dd, J=8.55, 5.19 Hz, 2 H) 7.09 (d, J=8.55 Hz, 1 H) 7.01-7.07 (m, 3 H) 6.86 (dd, J=8.39, 2.29 Hz, 1 H) 6.78 (s, 1 H) 5.94-6.05 (m, 1 H) 5.84-5.94 (m, 1 H) 4.84 (dt, J=17.70, 2.14 Hz, 1 H) 4.57-4.66 (m, 1 H) 4.50 (dd, J=8.39, 3.51 Hz, 1 H) 3.80 (s, 3 H) 2.82-2.95 (m, 1 H) 2.71-2.82 (m, 1 H).

Workup

  1. customThe flask was flushed with nitrogen
  2. customsealed
  3. temperatureThe reaction mixture was cooled to rt
  4. customThe mixture was flushed with nitrogen
  5. customsealed
  6. temperatureheated at 70° C. for an additional 24 h
  7. customThe crude reaction contents
  8. customthe product was purified

Sources & evidence

ORD record
ord-08b15716fc2b4f94952d59f2551fa0b4
Source dataset
uspto-grants-2013_01
Patent number
US08349880B2

Reaction notes

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