Pyridine → HCID 70663719, compound

HRID 1963050Notes

Reaction equation

HRID 1963050 reaction equation
[Cl:1][C:2]1[CH:23]=[CH:22][CH:21]=[C:20]([F:24])[C:3]=1[CH2:4][C:5]1[C:6]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)=[C:7]2[N:12]([CH:13]=1)[CH:11]=[CH:10][CH:9]=[CH:8]2.N1C=CC=CC=1.Cl[C:32](Cl)([O:34]C(=O)OC(Cl)(Cl)Cl)Cl.[C:43]([O:47][C:48]([N:50]1[CH2:55][CH2:54][NH:53][CH2:52][CH2:51]1)=[O:49])([CH3:46])([CH3:45])[CH3:44].C(N(CC)CC)C>C(Cl)Cl.Cl>[C:43]([O:47][C:48]([N:50]1[CH2:55][CH2:54][N:53]([C:32]([C:13]2[N:12]3[C:7]([CH:8]=[CH:9][CH:10]=[CH:11]3)=[C:6]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)[C:5]=2[CH2:4][C:3]2[C:20]([F:24])=[CH:21][CH:22]=[CH:23][C:2]=2[Cl:1])=[O:34])[CH2:52][CH2:51]1)=[O:49])([CH3:46])([CH3:44])[CH3:45]

Participants

8

Reactant 5

HCID 1049PyridineHCID 8471TriethylamineHCID 94429TriphosgeneHCID 143452tert-Butyl piperazine-1-carboxylateHCID 67772676HCID 67772676, compound

Product 1

HCID 70663719HCID 70663719, compoundYield 94.9%

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

The compound of step 2 (0.576 g, 1.72 mmol) was dissolved in DCM (8 ml) under argon and cooled at 0° C. Pyridine (0.14 ml, 1.72 mmol) and triphosgene (0.509 g, 1.72 mmol) were added and the mixture was stirred at room temperature for 2 h. The mixture was then added dropwise to a solution of 1-tert-butoxycarbonyl-piperazine (1.28 g, 6.85 mmol) and triethylamine (0.86 ml, 6.85 mmol) in DCM (8 ml) cooled to 0° C. The mixture stirred at room temperature overnight, then diluted with 1 N hydrochloric acid and extracted with DCM. The combined organic phases were washed with a saturated sodium hydrogencarbonate solution and twice with a saturated sodium chloride solution, were dried over sodium sulfate, filtered and evaporated to dryness. The residue was purified by silica gel chromatography (cyclohexane/EA, 100:0, then 75:25) to give 0.895 g of the title compound as an off-white powder.

Workup

  1. temperaturecooled to 0° C
  2. stirringThe mixture stirred at room temperature overnight
  3. extractionextracted with DCM
  4. washThe combined organic phases were washed with a saturated sodium hydrogencarbonate solution and twice with a saturated sodium chloride solution
  5. dry with materialwere dried over sodium sulfate
  6. filtrationfiltered
  7. customevaporated to dryness
  8. customThe residue was purified by silica gel chromatography (cyclohexane/EA, 100:0

Sources & evidence

ORD record
ord-9c483204dd594f9d9acd7ef1185c96b0
Source dataset
uspto-grants-2013_04
Patent number
US08415336B2

Reaction notes

Loading…