Acetic Acid → HCID 67470525, compound

HRID 2089641Notes

Reaction equation

HRID 2089641 reaction equation
[NH2:1][C:2](=[N:46][C:47]([O:49][CH2:50][C:51]([CH3:54])([CH3:53])[CH3:52])=[O:48])[C:3]1[CH:8]=[CH:7][C:6]([NH:9][C@H:10]([C:33]2[CH:38]=[C:37]([O:39][CH3:40])[CH:36]=[C:35]([O:41][CH2:42][CH2:43][OH:44])[C:34]=2[F:45])[C:11]2[N:12]=[C:13]([O:22][CH2:23][O:24][C:25]([CH:27]3[CH2:32][CH2:31][CH2:30][CH2:29][CH2:28]3)=[O:26])[N:14]([C:16]3[N:21]=[CH:20][CH:19]=[CH:18][N:17]=3)[N:15]=2)=[CH:5][CH:4]=1.C(N(CC)CC)C.CN(C(F)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[C:77](O)(=[O:79])[CH3:78]>CN(C1C=CN=CC=1)C.CN(C=O)C.ClCCl>[C:77]([O:44][CH2:43][CH2:42][O:41][C:35]1[C:34]([F:45])=[C:33]([C@@H:10]([NH:9][C:6]2[CH:5]=[CH:4][C:3]([C:2]([NH2:1])=[N:46][C:47]([O:49][CH2:50][C:51]([CH3:54])([CH3:53])[CH3:52])=[O:48])=[CH:8][CH:7]=2)[C:11]2[N:12]=[C:13]([O:22][CH2:23][O:24][C:25]([CH:27]3[CH2:28][CH2:29][CH2:30][CH2:31][CH2:32]3)=[O:26])[N:14]([C:16]3[N:21]=[CH:20][CH:19]=[CH:18][N:17]=3)[N:15]=2)[CH:38]=[C:37]([O:39][CH3:40])[CH:36]=1)(=[O:79])[CH3:78]

Participants

8

Reactant 4

HCID 176Acetic AcidHCID 8471TriethylamineHCID 2774761Tetramethylfluoroformamidinium hexafluorophosphateHCID 68213002HCID 68213002, compound

Product 1

HCID 67470525HCID 67470525, compound

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×

Procedure

Cyclohexanecarboxylic acid 5-{(R)-(4-{amino[2,2-dimethylpropoxycarbonylimino]methyl}phenylamino)-[2-fluoro-3-(2-hydroxyethoxy)-5-methoxyphenyl]methyl}-2-pyrimidin-2-yl-2H-[1,2,4]-triazol-3-yloxymethyl ester (42 mg), DMAP (1 mg), and triethylamine (0.0648 mL) were dissolved in DMF (3 mL) and dichloromethane (3 mL). To the solution, a mixture of TFFH (30.7 mg), acetic acid (0.00665 mL), and dichloromethane (3 mL) was slowly added, and the resulting mixture was stirred at room temperature for 3 hours. After concentrating the reaction mixture under reduced pressure, ice, THF, saturated aqueous sodium hydrogen carbonate solution, and saturated aqueous ammonium chloride solution were added to the residue obtained, and the resulting mixture was extracted with a mixture of THF and ethyl acetate. The organic layer was washed with saturated aqueous ammonium chloride solution and dried over anhydrous magnesium sulfate. The resulting mixture was filtered, and the filtrate obtained was concentrated under reduced pressure. The residue obtained was crudely purified by NAM silica gel column chromatography (mixed solvent of methanol-ethyl acetate) to obtain a crudely purified product of the captioned compound.

Workup

  1. additionwas slowly added
  2. concentrationAfter concentrating the reaction mixture under reduced pressure, ice, THF, saturated aqueous sodium hydrogen carbonate solution, and saturated aqueous ammonium chloride solution
  3. additionwere added to the residue
  4. customobtained
  5. extractionthe resulting mixture was extracted with a mixture of THF and ethyl acetate
  6. washThe organic layer was washed with saturated aqueous ammonium chloride solution
  7. dry with materialdried over anhydrous magnesium sulfate
  8. filtrationThe resulting mixture was filtered
  9. customthe filtrate obtained
  10. concentrationwas concentrated under reduced pressure
  11. customThe residue obtained
  12. customwas crudely purified by NAM silica gel column chromatography (mixed solvent of methanol-ethyl acetate)
  13. customto obtain a crudely purified product of the captioned compound

Sources & evidence

ORD record
ord-73dce4a6bfa44c0dbeb3f79c37bf0164
Source dataset
uspto-grants-2013_05
Patent number
US08436009B2

Reaction notes

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