Trifluoroacetic acid → HCID 86649937, compound

HRID 1803308Notes

Reaction equation

HRID 1803308 reaction equation
[F:1][C:2]([F:7])([F:6])[C:3]([OH:5])=[O:4].[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(=O)C[CH2:29][N:23]4[N:22]=3)=[CH:16][C:15]=2[O:39][CH3:40])[CH:13]=1.CCN(S(F)(F)F)CC.[C:50](O)([C:52]([F:55])(F)[F:53])=O>C([O-])(O)=O.[Na+]>[F:1][C:2]([F:7])([F:6])[C:3]([OH:5])=[O:4].[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:52]([F:55])([F:53])[CH2:50][CH2:29][N:23]4[N:22]=3)=[CH:16][C:15]=2[O:39][CH3:40])[CH:13]=1

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 123472(Diethylamino)sulfur trifluorideHCID 66860172HCID 66860172, compound

Product 1

HCID 86649937HCID 86649937, compoundYield 6%

Reagents, catalysts & solvents 1

HCID 516892Sodium BicarbonateSolvent

Conditions

Temperature
0 °C

Procedure

To a 10 mL round bottomed flask was added 2-(4-(4-chloro-1H-imidazol-1-yl)-3-methoxyphenylamino)-9-(4-fluorophenyl)-8,9-dihydro-5H-[1,2,4]triazolo[1,5-a]azepin-7(6H)-one (100 mg, 0.214 mmol, from Example 137). The vessel was purged with nitrogen. DCM (1 mL) was added and the solution was cooled to 0° C. DAST (0.071 mL, 0.535 mmol) was added and the stirred reaction mixture was allowed to slowly warm to ambient temperature. After 18 h, saturated aqueous NaHCO3 (200 mL) was carefully added, and the mixture was extracted with EtOAc (300 mL). The organics were washed with brine (100 mL), dried over sodium sulfate, filtered, and concentrated in vacuo. The crude product was purified using reverse phase preparatory HPLC (MeOH/water/trifluoroacetic acid) to afford the titled compound (8.2 mg, 6% yield) as a TFA salt. LC-MS (M+H)+ 489.2. 1H NMR (500 MHz, CHLOROFORM-d) δ ppm 9.14 (1 H, br. s.), 8.11 (1 H, s), 7.03-7.45 (7 H, m), 4.59 (1 H, br. s.), 4.26-4.46 (2 H, m), 3.87 (3 H, s), 2.29-2.84 (4 H, m).

Workup

  1. customThe vessel was purged with nitrogen
  2. additionDCM (1 mL) was added
  3. customthe stirred reaction mixture
  4. temperatureto slowly warm to ambient temperature
  5. extractionthe mixture was extracted with EtOAc (300 mL)
  6. washThe organics were washed with brine (100 mL)
  7. dry with materialdried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customThe crude product was purified

Sources & evidence

ORD record
ord-a212fab488f44e0184a18d7093813bfd
Source dataset
uspto-grants-2013_01
Patent number
US08349880B2

Reaction notes

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