Trifluoromethanesulfonic anhydride → HCID 69767203, compound

HRID 1386815Notes

Reaction equation

HRID 1386815 reaction equation
O[CH2:2][CH:3]1[CH2:8][CH2:7][N:6]([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:5][CH2:4]1.S(OS(C(F)(F)F)(=O)=O)(C(F)(F)F)(=O)=O.FC1(CCCC2C=CC=CC=2)CCN(C[C@@H]2[C@@H](C3C=CC=C(F)C=3)CN([C@H](C(C)C)C(O)=O)C2)CC1.C(N(C(C)C)CC)(C)C.[CH2:76]([C:78]1[NH:88][C:81]2=[N:82][C:83]([CH3:87])=[CH:84][C:85]([CH3:86])=[C:80]2[N:79]=1)[CH3:77]>C(Cl)Cl.CCOCC>[CH2:76]([C:78]1[N:88]([CH2:2][CH:3]2[CH2:8][CH2:7][N:6]([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:5][CH2:4]2)[C:81]2=[N:82][C:83]([CH3:87])=[CH:84][C:85]([CH3:86])=[C:80]2[N:79]=1)[CH3:77]

Participants

8

Reactant 5

HCID 67749Trifluoromethanesulfonic anhydrideHCID 81531DiisopropylethylamineHCID 2764081Tert-butyl 4-(hydroxymethyl)piperidine-1-carboxylateHCID 20672401HCID 20672401, compoundHCID 178437439HCID 178437439, compound

Product 1

HCID 69767203HCID 69767203, compoundYield 19.5%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
-78 °C

Procedure

To a solution of 0.216 g of 4-hydroxymethyl-piperidine-1-carboxylic acid, tert-butyl ester (from Step B) in 6 mL of CH2Cl2 at −78° C. was added 0.202 mL of triflic anhydride. After stirring at −78° C. for 5 minutes, 0.151 mL of 2, 6-lutidine was added dropwise. The temperature was maintained below −70° C. throughout the reaction. After stirring for 15 minutes, 0.35 mL of diisopropylethylamine was added dropwise. After 15 minutes, a solution of 0.35 g 2-ethyl-5,7-dimethyl-3-H-imidazo[4,5-b]pyridine (prepared as described by Mantlo et al. U.S. Pat. No. 5, 412,097 and J. Med. Chem. 1991, 34, 2919 ) in 4 mL of CH2Cl2 was added dropwise. After warming to 0° C., the reaction was stirred at rt for 5 hr. The reaction was diluted with Et2O, then washed with H2O. The aqueous phase was extracted with 2×25 mL Et2O. The combined organic phases were dried over MgSO4 and concentrated. The residue was purified by flash chromatography eluting with 50% EtOAc in hexane to give 73 mg of the title compound as an oil.

Workup

  1. temperatureThe temperature was maintained below −70° C. throughout the reaction
  2. stirringAfter stirring for 15 minutes
  3. waitAfter 15 minutes
  4. temperatureAfter warming to 0° C.
  5. stirringthe reaction was stirred at rt for 5 hr
  6. washwashed with H2O
  7. extractionThe aqueous phase was extracted with 2×25 mL Et2O
  8. dry with materialThe combined organic phases were dried over MgSO4
  9. concentrationconcentrated
  10. customThe residue was purified by flash chromatography
  11. washeluting with 50% EtOAc in hexane

Sources & evidence

ORD record
ord-3b19d59d19ea45bc95cd457c12f6fba0
Source dataset
uspto-grants-2001_07
Patent number
US06265434B1

Reaction notes

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