HCID 66859881, compound → HCID 58110156, compound

HRID 1803305Notes

Reaction equation

HRID 1803305 reaction equation
FC(F)(F)C(O)=O.[Cl:8][C:9]1[N:10]=[CH:11][N:12]([C:14]2[CH:19]=[CH:18][C:17]([NH:20][C:21]3[N:38]=[C:24]4[CH:25]([C:31]5[CH:36]=[CH:35][C:34]([F:37])=[CH:33][CH:32]=5)[CH2:26][C:27](=[CH2:30])[CH2:28][CH2:29][N:23]4[N:22]=3)=[CH:16][C:15]=2[O:39][CH3:40])[CH:13]=1>C(O)C.[Pt]>[Cl:8][C:9]1[N:10]=[CH:11][N:12]([C:14]2[CH:19]=[CH:18][C:17]([NH:20][C:21]3[N:38]=[C:24]4[CH:25]([C:31]5[CH:36]=[CH:35][C:34]([F:37])=[CH:33][CH:32]=5)[CH2:26][CH:27]([CH3:30])[CH2:28][CH2:29][N:23]4[N:22]=3)=[CH:16][C:15]=2[O:39][CH3:40])[CH:13]=1

Participants

4

Reactant 1

HCID 66859881HCID 66859881, compound

Product 1

HCID 58110156HCID 58110156, compoundYield 74%

Reagents, catalysts & solvents 2

HCID 23939PlatinumCatalystHCID 702EthanolSolvent

Conditions

Temperature
0 °C

Procedure

N-(4-(4-chloro-1H-imidazol-1-yl)-3-methoxyphenyl)-9-(4-fluorophenyl)-7-methylene-6,7,8,9-tetrahydro-5H-[1,2,4]triazolo[1,5-a]azepin-2-amine (65 mg, 0.140 mmol, from example 133) was dissolved in ethanol (5 mL), flushed with nitrogen, and chilled to 0° C. Platinum on sulfided carbon (136 mg, 0.140 mmol) was added and the flask was repeated evacuated and flushed with hydrogen gas (balloon). The reaction mixture was stirred under an atmosphere of hydrogen gas at rt for 16 h. The reaction mixture was purged with nitrogen, filtered over celite. The celite was washed with methanol and the combined filtrates were concentrated in vacuo. The crude product was purified using reverse phase preparatory HPLC (AcCN/water/ammonium acetate) to afford the titled compound as a mixture of diasteromers (51.6 mg, 74% yield). LC-MS (M+H)+ 467.2. 1H NMR (500 MHz, CHLOROFORM-d, mixture of diastereomers) δ ppm 7.53 (1 H, dd, J=16.2, 1.5 Hz), 7.41 (1 H, t, J=2.1 Hz), 7.29-7.34 (1 H, m), 6.95-7.16 (5 H, m), 6.71-6.79 (1 H, m), 4.62 (1 H, br. s.), 3.96-4.16 (1 H, m), 3.73-3.88 (3 H, m), 2.00-2.10 (2 H, m), 1.91 (1 H, dd, J=14.2, 6.6 Hz), 1.71-1.85 (1 H, m), 1.50-1.68 (2 H, m), 1.09 (3 H, dd, J=16.9, 6.6 Hz).

Workup

  1. customflushed with nitrogen
  2. customthe flask was repeated evacuated
  3. customflushed with hydrogen gas (balloon)
  4. customThe reaction mixture was purged with nitrogen
  5. filtrationfiltered over celite
  6. washThe celite was washed with methanol
  7. concentrationthe combined filtrates were concentrated in vacuo
  8. customThe crude product was purified

Sources & evidence

ORD record
ord-9da4a91e58bf4233ab774033c60d0209
Source dataset
uspto-grants-2013_01
Patent number
US08349880B2

Reaction notes

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