Triethylamine → HCID 86268829, compound

HRID 718203Notes

Reaction equation

HRID 718203 reaction equation
[NH:1]([C:3]1[N:8]=[C:7]([CH3:9])[C:6]([O:10][C:11]2[CH:16]=[CH:15][N:14]=[C:13]([C:17]3[CH:18]=[N:19][N:20]([CH3:22])[CH:21]=3)[CH:12]=2)=[CH:5][CH:4]=1)[NH2:2].[CH3:23][C:24]([CH3:29])([CH3:28])[C:25](Cl)=[O:26].C(N(CC)CC)C.Cl[C:38](Cl)([O:40]C(=O)OC(Cl)(Cl)Cl)Cl>C(Cl)Cl>[C:24]([C:25]1[O:26][C:38](=[O:40])[N:1]([C:3]2[CH:4]=[CH:5][C:6]([O:10][C:11]3[CH:16]=[CH:15][N:14]=[C:13]([C:17]4[CH:18]=[N:19][N:20]([CH3:22])[CH:21]=4)[CH:12]=3)=[C:7]([CH3:9])[N:8]=2)[N:2]=1)([CH3:29])([CH3:28])[CH3:23]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 62493Pivaloyl chlorideHCID 94429TriphosgeneHCID 90446486HCID 90446486, compound

Product 1

HCID 86268829HCID 86268829, compoundYield 107.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Procedure

A mixture of Example A4 (0.20 g, 0.67 mmol) in DCM (4 mL) was cooled in an ice-water bath and treated with trimethylacetyl chloride (0.16 g, 1.35 mmol). The mixture was allowed to warm up to RT and stirred for 30 min. The reaction mixture was cooled to 0° C. and then diluted with DCM (4 mL). Triethylamine (0.5 mL, 3.61 mmol) was added and then a solution of triphosgene (80 mg, 0.26 mmol) in DCM (4 mL) was added drop-by-drop under the same conditions. The reaction mixture was allowed to warm to RT and stirred at RT overnight. The mixture was quenched with NaHCO3 solution and extracted with DCM (2×). The organic was dried over Na2SO4, filtered and concentrated in vacuo. The crude product was purified via silica gel chromatography (EtOAc) to obtain 5-(tert-butyl)-3-(6-methyl-5-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyridin-2-yl)-1,3,4-oxadiazol-2(3H)-one (114 mg, 37.8%). 1H NMR (400 MHz, DMSO-d6): δ 8.39 (d, J=5.7 Hz, 1H), 8.27 (s, 1H), 7.97 (s, 1H), 7.78 (d, J=8.7 Hz, 1H), 7.70 (d, J=8.8 Hz, 1H), 7.23 (d, J=2.4 Hz, 1H), 6.67 (dd, J=5.7, 2.4 Hz, 1H), 3.85 (s, 3H), 2.37 (s, 3H), 1.33 (s, 9H); MS (ESI) m/z: 407.2 (M+H+).

Workup

  1. temperatureThe reaction mixture was cooled to 0° C.
  2. temperatureto warm to RT
  3. stirringstirred at RT overnight
  4. customThe mixture was quenched with NaHCO3 solution
  5. extractionextracted with DCM (2×)
  6. dry with materialThe organic was dried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe crude product was purified via silica gel chromatography (EtOAc)

Sources & evidence

ORD record
ord-adf9da915e7746608cbd179c1e492a33
Source dataset
uspto-grants-2015_11
Patent number
US09193719B2

Reaction notes

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